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The field of gene therapy using Adeno-associated viral (AAV) vector delivery is rapidly advancing in the biotherapeutics industry. Despite its successes, AAV manufacturing remains a challenge due to limited production yields. The triple plasmid transfection of HEK293 cells represents the most extensively utilized system for AAV production. The regulatory factors and mechanisms underlying viral production in HEK293 cells are largely unknown. In this study, we isolated high-titer AAV production clones from a parental HEK293 population using a single limiting dilution step, and subsequently elucidating their underlying molecular mechanisms through whole transcriptome analysis. LncRNA TCONS_00160397 was upregulated in clones and shown to promoted HEK293 cells proliferation and improved the titer of AAV production. Mechanistically, results from proteomics and metabolomics indicated that TCONS_00160397 regulated the ABC transporters pathway. These findings furnish a rich repository of knowledge and actionable targets for the rational optimization of HEK293-based producer lines, thereby paving the way for tangible improvements in AAV vector output and expediting the broad implementation of gene therapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Long non-coding RNAs (lncRNAs) play important roles in progression of neuroblastoma (NB). LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been shown to affect the development of multiple tumors. However, the effect of NEAT1 on NB remain unclear. In this study, the new mechanisms whereby how NEAT1 influences tumor progression in NB was investigated., Methods: RT-qPCR, western blot, bioinformatics, cell growth, Transwell, and flow cytometric analyses were performed to determine how NEAT1 synchronously regulates the miR-873-5p/MYCN proto-oncogene(MYCN) and miR-873-5p/polypeptide N-acetylgalactosaminyltransferase 1(GalNAcT-I) axes to accelerate the progression of NB. NB-bearing animal models were established to evaluate the function of NEAT1 in NB. The relationships between transcription factor coactivatorassociated arginine methyltransferase 1 (CARM1) and NEAT1, NEAT1 and miR-873-5p, miR-873-5p and GalNacT-I or MYCN, were verified using luciferase reporter gene assay, respectively., Results: Our study revealed elevated levels of NEAT1 expression in NB cells and tissues which was associated with an advanced pathological stage and poor prognostic outcomes. According to in vitro gain- and loss- of function experiments, NEAT1 enhances progression of NB. NEAT1 silencing was found to inhibit NB proliferation in vivo. Mechanistically, to achieve upstream regulation, epigenetic downregulation of NEAT1 was achieved via the inhibition of CARM1. NEAT1 was found to positively regulate MYCN and GalNAcT-I levels as a competitive sponge of miR-873-5p., Conclusion: Activity of the lncRNA NEAT1 can be triggered via CARM1, which synchronously promotes NB development via the miR-873-5p/MYCN and miR-873-5p/GalNAcT-I axes. These findings shed light on the novel molecular mechanisms underlying NB progression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of LncRNA SNHG20 on epithelial mesenchymal transition (EMT) and microtubule formation in human oral squamous cell carcinoma (OSCC) cells through targeted regulation of the miR-520c-3p/ RAB22A pathway., Methods: After real-time fluorescence quantitative detection of LncRNA SNHG20, miR-520c-3p, RAB22A mRNA expression levels in OSCC tissues and cells, dual luciferase reporter assay was used to detect the relationship between the three. OSCC cells were randomly separated into control group, sh-NC group, sh-SNHG20 group, sh-SNHG20+anti NC group, and sh-SNHG20+anti miR-520c-3p group. Western blotting was used to detect the expression of N-cadherin, vimentin, and E-cadherin proteins in the OSCC cells. The morphology of HSC-3 cells was observed under microscope. Changes in the number of microtubules formed were detected. The effect of LncRNA SNHG20 on the growth of OSCC tumors and the expression levels of LncRNA SNHG20, miR-520c-3p and RAB22 A in the transplanted tumors were detected by nude mice tumorigenesis experiment., Results: LncRNA SNHG20 and RAB22A mRNA were upregulated in the OSCC tissues and cells, while miR-520c-3p was downregulated ( P < 0.05). There were binding sites between LncRNA SNHG20 and miR-520c-3p, RAB22A and miR-520c-3p, which had targeted regulation relationship. Compared with the sh-NC group, the sh-SNHG20 group had fewer stromal like cells, more epithelial like cells, incomplete microtubule structure, and fewer nodules. LncRNA SNHG20, RAB22A, N-Cadherin, and vimentin were downregulated, while miR-520c-3p and E-cadherin were upregulated ( P < 0.05). Compared with the sh-SNHG20+anti-NC group, the sh-SNHG20+anti-miR-520c-3p group had a higher number of stromal like cells, a lower number of epithelioid cells, tighter microtubule arrangement, and more microtubule nodules. miR-520c-3p and E-cadherin were downregulated, while RAB22A, N-cadherin, and vimentin were upregulated ( P < 0.05). The transplanted tumor of OSCC in sh-SNHG20 group was smaller and lower than that in sh-NC group. The expression levels of LncRNA SNHG20 and RAB22A in the transplanted tumor tissues were lower than those in sh-NC group, and the expression level of miR-520c-3p was higher than that in sh-NC group ( P < 0.05)., Conclusion: LncRNA SNHG20 promotes epithelial-mesenchymal transition and microtubule formation in human oral squamous cell carcinoma cells by targeting the miR-520c-3p/ RAB22A pathway. Inhibiting the expression of LncRNA SNHG20 can target and regulate the miR-520c-3p/ RAB22A pathway to inhibit EMT and microtubule formation in OSCC cells.

Ischemic stroke (IS) is a severe and sudden cerebrovascular event, associated with notably high rates of mortality and morbidity. The process of apoptosis, a genetically orchestrated form of programmed cell death, is divided into two pathways: intrinsic and extrinsic. The intricate involvement of long non-coding RNA (lncRNA) in the pathobiology of IS, particularly in modulating neuronal apoptosis, is a burgeoning area of research. This review synthesizes the current understanding of the regulatory mechanisms of lncRNA on neuronal apoptosis in the context of ischemic stroke. Specifically, we highlight the roles of lncRNA such as ANRIL, C2dat1/2, H19, TUG1, MEG3, SNHG, and GAS5, which have been implicated in the facilitation of neuronal apoptosis. Conversely, the lncRNA N1LR has been shown to exert an inhibitory effect on this process. The role of MALAT1 in neuronal apoptosis remains a subject of ongoing debate, as its function oscillates between pro-apoptotic and anti-apoptotic roles, thus highlighting the need for further elucidation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Gastric cancer (GC) has been ranked as the third incidence tumors globally. Long non-coding RNA (lncRNA) NRAV has been reported as a tumor-enhancer in the development of human cancers, whereas the function of NRAV in GC remains to be elucidated. The aim of this research was to explore the underlying function of NRAV in GC. Through comprehensive bioinformatics analysis, a significantly elevation of NRAV was found in both human GC tissues and cell lines, which indicated the poor prognosis of GC patients. Then, we conducted a series of functional experiments to illustrate the role of NRAV in GC. The results showed that the down-regulation of NRAV exhibited a significant inhibitory effect on GC cell proliferation and migration, while NRAV overexpression promoted GC cell proliferation and migration. Through xenograft mouse tumor model, the suppression of NRAV led to a reduction in the growth of tumor mice, whereas overexpression of NRAV notably enhanced tumor growth. Finally, EFHC1 was revealed as the potential target gene of NRAV. Overall, our findings indicated the promising application of NRAV as a therapeutic target and prognostic biomarker for GC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Colorectal cancer (CRC) represents a common type of carcinoma with significant mortality rates globally. A primary factor contributing to the unfavorable treatment outcomes and reduced survival rates in CRC patients is the occurrence of metastasis. Various intricate molecular mechanisms are implicated in the metastatic process, leading to mortality among individuals with CRC. In the realm of intercellular communication, exosomes, which are a form of extracellular vesicle (EV), play an essential role. These vesicles act as conduits for information exchange between cells and originate from multiple sources. By fostering a microenvironment conducive to CRC progression, exosomes and EVs significantly influence the advancement of the disease. They contain a diverse array of molecules, including messenger RNAs (mRNAs), non-coding RNAs (ncRNAs), proteins, lipids, and transcription factors. Notably, ncRNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are prominently featured within exosomes. These ncRNAs have the capacity to regulate various critical molecules or signaling pathways, particularly those associated with tumor metastasis, thereby playing a crucial role in tumorigenesis. Their presence indicates a substantial potential to affect vital aspects of tumor progression, including proliferation, metastasis, and resistance to treatment. This research aims to categorize exosomal ncRNAs and examine their functions in colorectal cancer. Furthermore, it investigates the clinical applicability of novel biomarkers and therapeutic strategies in CRC. Abbreviations: ncRNAs, non-coding RNAs; CRC, Colorectal cancer; EV, extracellular vesicle; mRNAs, messenger RNAs; miRNAs, microRNAs; lncRNAs, long non-coding RNAs; circRNAs, circular RNAs; HOTTIP, HOXA transcript at the distal tip; NSCLC, non-small cell lung cancer; 5-FU, 5-fluorouracil; OX, Oxaliplatin; PDCD4, programmed cell death factor 4; Tregs, regulatory T cells; EMT, epithelial-mesenchymal transition; PFKFB3, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3; USP2, ubiquitin carboxyl-terminal hydrolase 2; TNM, tumor node metastasis; TAMs, tumor-associated macrophages; RASA1, RAS p21 protein activator 1; PDCD4, programmed cell death 4; ZBTB2, zinc finger and BTB domain containing 2; SOCS1, suppressor of cytokine signaling 1; TUBB3, β-III tubulin; MSCs, mesenchymal stem cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Deep venous thrombosis (DVT) is a kind of vascular obstruction, that commonly and widely occurs in lower limbs. Due to the lack of obvious symptoms in the early stage, the rate of misdiagnosis and missed diagnosis is high. This study evaluated the expression and significance of lncRNA ASB16-AS1 (ASB16-AS1) in DVT aiming to identify a novel biomarker for its screening and monitoring., Methods: There were 77 DVT patients and 62 healthy individuals included in this study. Plasma ASB16-AS1 level was evaluated using PCR and compared between DVT and healthy groups. The diagnostic and prognostic values of ASB16-AS1 were assessed with ROC and Cox analyses. The correlation of ASB16-AS1 with patients' conditions, inflammation, and oxidative stress was evaluated by Spearman correlation analysis., Results: ASB16-AS1 was significantly upregulated in DVT (P < 0.001), which could discriminate DVT patients from healthy individuals with high sensitivity and specificity (AUC of ROC = 0.858). Increased ASB16-AS1 was associated with the incidence of complications (P = 0.033) and especially for pulmonary embolism in patients (P = 0.029). ASB16-AS1 was negatively correlated with prothrombin time (PT, r = -0.763), antithrombin level (AT, r = -0.711), and international normalized ratio (INR, r = -0.764), and showed positive correlation with fibrinogen (FIB, r = 0.793) and D-dimer (D-D, r = 0.731). Additionally, ASB16-AS1 was positively correlated with pro-inflammation cytokines (r IL-6 = 0.853, r IL-10 = -0.836, r hsCRP = 0.787) and pro-oxidative stress factors (r SOD = -0.751, r MDA = 0.842, r 8-isoPGF 2α = 0.840)., Conclusion: Upregulated ASB16-AS1 was identified as a diagnostic and prognostic biomarker of DVT and was closely associated with inflammation and oxidative stress during DVT., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by The Ethics Committee of Zibo Central Hospital (No. 201711010) and followed the principles outlined in the Declaration of Helsinki. In addition, informed consent has been obtained from the participants involved. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: Not Applicable., (© 2025. The Author(s).)

RNA-based therapeutics highlighted novel approaches to target either coding or noncoding molecules for multiple diseases treatment. In breast cancer (BC), a multitude of deregulated long noncoding RNAs (lncRNAs) have been identified as potential therapeutic targets also in the context of antiestrogen resistance, and the RNA binding activity of the estrogen receptor α (ERα) points additional potential candidates to interfere with estrogenic signaling. A set of lncRNAs was selected among ERα-associated RNAs in BC cell nuclei due to their roles in processes such as transcriptional regulation and epigenetic chromatin modifications. Native immunoprecipitation of nuclear ERα-interacting RNAs coupled to NGS (RIP-Seq) was performed in MCF-7 cells, leading to the identification of essential lncRNAs interacting with the receptor in multi-molecular regulatory complexes. Among these, PVT1, FGD5-AS1 and EPB41L4A-AS1 were selected for further investigation. Functional assays and transcriptome analysis following lncRNA knock-down indicated PVT1 as the master modulator of some of the most relevant BC hallmarks, such as cell proliferation, apoptosis, migration and response to hypoxia. In addition, targeted experiments identified PVT1 as a key factor in the composition of PRC2-ERα network involved in downregulation of tumor suppressor genes, including BTG2., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods were performed in accordance with the relevant guidelines and regulations concerning good scientific practice. The study did not require ethical approval as it did not include live vertebrates or human participants., (© 2025. The Author(s).)

Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by loss-of-function mutations in the MECP2 gene, resulting in diverse cellular dysfunctions. Here, we investigated the role of the long noncoding RNA (lncRNA) NEAT1 in the context of MeCP2 deficiency using human neural cells and RTT patient samples. Through single-cell RNA sequencing and molecular analyses, we found that NEAT1 is markedly downregulated in MECP2 knockout (KO) cells at various stages of neural differentiation. NEAT1 downregulation correlated with aberrant activation of the mTOR pathway, abnormal protein metabolism, and dysregulated autophagy, contributing to the accumulation of protein aggregates and impaired mitochondrial function. Reactivation of NEAT1 in MECP2-KO cells rescued these phenotypes, indicating its critical role downstream of MECP2. Furthermore, direct RNA-RNA interaction was revealed as the key process for NEAT1 influence on autophagy genes, leading to altered subcellular localization of specific autophagy-related messenger RNAs and impaired biogenesis of autophagic complexes. Importantly, NEAT1 restoration rescued the morphological defects observed in MECP2-KO neurons, highlighting its crucial role in neuronal maturation. Overall, our findings elucidate lncRNA NEAT1 as a key mediator of MeCP2 function, regulating essential pathways involved in protein metabolism, autophagy, and neuronal morphology., (© The Author(s) 2025. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancer types around the world. Although OSCC can be diagnosed or monitored through tissue biopsy, this invasive procedure could cause considerable pain and discomfort to patients. As a preferable alternative, liquid biopsy offers less invasive diagnostics. In our study to enhance OSCC detection, we analyzed cell-free RNA (cfRNA) transcriptomes (mRNA, lncRNA) from blood (plasma) and saliva samples of individuals in three groups: OSCC group, oral benign tumor group, and a normal control group. Our transcriptomic profiling revealed that in the saliva group, CLEC2B was notably upregulated in the OSCC group compared to others, while DAZL, F9, and AC008735.2 were markedly downregulated. However, no OSCC-specific RNAs were identified in the blood (plasma) samples. Furthermore, OSCC group showed a higher neutrophil infiltration and lower B cells, CD4 + T cells (non-regulatory) and regulatory T cell (Tregs) infiltration in oral saliva environment when compared to the control groups. This study suggests that saliva might be a better liquid biopsy medium over blood (plasma) for cfRNA on detecting OSCC. CLEC2B, DAZL, F9, and AC008735.2 in saliva may serve as potential diagnostic liquid biomarkers for OSCC, warranting further investigation., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: Approval of the research protocol by an Institutional Reviewer Board: Ethical approval for this study was granted by the Ethics Committee of Cancer Hospital of Shantou University Medical College (Approval No. 2024017). Informed consent: All informed consent was obtained from the subjects and/or guardians., (© 2025. The Author(s).)

Long noncoding RNAs (lncRNAs) are closely associated with tumor development, and increasing evidence suggests that small open reading frame (smORF) within lncRNAs also have the capability to encode smORF-encoded peptides (SEPs). Here, we thoroughly uncovered the SEP expression profile of hepatocellular carcinoma (HCC) from tumor and adjacent nontumor tissues of 154 HCC patients using high-throughput mass spectrometry (MS). A total of 208 SEPs were identified, with no significant difference in abundance and stability compared with coding region proteins. Notably, the peptide encoded by LINC01007 (LINC01007-33AA) was significantly upregulated in HCC tissues ( p < 0.05) and could serve as an independent risk factor affecting prognosis (HR [95% CI]: 1.31[1.01-1.7]). This endogenous peptide was further confirmed at both the mRNA and protein levels, and its overexpression significantly enhances the invasion and migration of HCC cells. These findings highlight the potential of MS-based methods to identify novel noncoding sequence encoded functional peptides associated with tumor progression.

Objectives: The purpose of this study was to determine the relationship between protein-coding RNA (messenger RNA, mRNA) and long noncoding RNA (lncRNA) expressed in vascular endothelial cells (VECs) in keloids by reanalyzing Gene Expression Omnibus (GEO) microarray chip data., Materials and Methods: The GSE121618 database and clinical information of these samples were downloaded and reanalyzed by the R language package. Expression differences in mRNA and lncRNA between keloids and normal skin were calculated. GO/KEGG enrichment analysis was conducted to determine the function of these genes, and an interaction network of lncRNAs-mRNAs was constructed. Magnetic Sorting of VECs and qRT-PCR were used to verify these bioinformatic results., Results: The expression of three hundred and five mRNAs in the keloid group was significantly different from that in the normal group, and 98 lncRNAs were different, 21 of which were upregulated and 118 of which were downregulated. The hub relationship between the upregulated lncRNA‒mRNA interaction was lncRNA LINC01546-RASAL3/COL13A1, while the downregulated hub was lncRNA LOC101929787-PRKAA2/KRT71/SSTR1. qPCR verification result showed no obvious statistical differences., Conclusions: Through the in-depth mining of keloid microarray data using bioinformatic methods, we speculated that VECs can affect the development and progression of keloids by epigenomic regulation via lncRNA‒mRNA interactions., Competing Interests: Declarations. Ethics approval and consent to participate: All applicable international, national, and/or institutional guidelines for the care and use of human tissue were followed. Informed consent was signed by all patients who provided samples for use in the experiment, which had been approved by IEC for Clinical Research and Animal Trials of the First Affiliated Hospital of Sun Yat-sen University (NO.[2023]291). Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Small nucleolar RNA host gene (SNHG) family were reported involved in various biological processes and may be used as a promising prognostic marker in esophageal cancer (EC). A meta-analysis was performed to investigate the relationship between SNHG expression and prognosis of EC in this study., Methods: Relevant databases were browsed to obtain suitable publications. Hazard ratio (HR) with 95% confidence interval (CI) were extracted to explore the association between SNHG expression and EC prognosis. Odds ratio (OR) with 95%CI were extracted to assess the association between SNHG expression and other clinicopathological parameters. Sensitivity analysis and publication bias were performed to explore the reliability and robustness of the results. Bio-informatics has been explored in order to confirm our conclusions more comprehensively., Results: 16 studies comprising 1229 patients were enrolled. The results showed that increasing SNHG expression indicated worse overall survival (HR: 1.392, 95%CI = 0.876-1.908). SNHG2, SNHG5, and SNHG12 were down-regulated, while other SNHGs were up-regulated in EC. In populations with low expression of SNHG2, SNHG5, and SNHG12, increasing SNHG expression predicted a favorable cancer prognosis (HR: 0.511, 95%CI = 0.322-0.700). Conversely, in populations with high expression of other SNHGs, SNHG expression indicated poor prognosis (OR: 2.340, 95%CI = 1.744-2.936). Elevated SNHG expression also implied advanced TNM stage (OR 1.578, 95%CI = 1.273-1.956) and lymph node metastasis (OR: 1.533, 95%CI = 1.205-1.950)., Conclusion: Increased expression of SNHG2, SNHG5, and SNHG12, and decreased expression of other SNHGs tended to have a favorable prognosis in patients with EC. These findings suggest that SNHG may serve as a prognostic marker and therapeutic target for EC., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: SEPN1, a selenoprotein involved in redox regulation and endoplasmic reticulum stress response, has an unclear role in cancer. This study aims to investigate the expression, prognostic significance, and tumor microenvironment (TME) relevance of SEPN1 across pan-cancer, with a particular focus on glioma., Methods: We analyzed SEPN1 expression and prognosis using the TCGA pan-cancer cohort. SEPN1 in glioma was further examined using data from TCGA, CGGA, GEO, and ZN-GC cohorts, along with survival analysis, single-cell RNA sequencing analysis, and enrichment analysis. We developed an SEPN1-related risk score (SRS) based on SEPN1-related long non-coding RNAs and validated its prognostic value. Drug sensitivity data and connectivity map analysis identified potential anti-glioma drugs based on the SRS., Results: We found that SEPN1 was significantly upregulated in glioma, associated with poor prognosis, functioned as an independent risk factor, and predominantly expressed in malignant glioma cells. Enrichment analysis indicated the involvement of SEPN1 in immune-related processes and signaling pathways. Suppressing SEPN1 in glioblastoma cells inhibited proliferation and induced G2/M arrest and apoptosis. The SRS demonstrated strong prognostic value and correlated with enhanced immune infiltration in the glioma TME. Potential anti-glioma drugs were identified based on the SRS., Conclusions: SEPN1 emerges as a novel biomarker and therapeutic target in glioma, providing a basis for future development of targeted therapies., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cancer stem cells (CSCs) are key drivers of cancer progression and therapeutic resistance. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of CSC properties. The aim of this study was to investigate the role of MIR4435-2HG in regulating CSC characteristics, tumorigenesis, and chemoresistance in pancreatic cancer. Functional assays were conducted to evaluate CSC self-renewal, tumorigenic potential, and chemoresistance in pancreatic cancer cells with altered expression of MIR4435-2HG. RNA interference (RNAi) was employed to knock down MIR4435-2HG, and a STAT1 reintroduction model was established to examine downstream signaling pathways. The role of miR-1252-5p as a competing endogenous RNA was also explored. Overexpression of MIR4435-2HG significantly enhanced CSC self-renewal and tumorigenic potential, whereas silencing MIR4435-2HG notably diminished these properties. Mechanistically, MIR4435-2HG promoted STAT1 expression by sponging miR-1252-5p, thereby enhancing CSC stemness and tumorigenesis. Moreover, depletion of MIR4435-2HG sensitized pancreatic cancer cells to gemcitabine-induced growth inhibition and ferroptosis. Reintroduction of STAT1 restored gemcitabine resistance in MIR4435-2HG-deficient cells. Our findings demonstrate that MIR4435-2HG plays a critical role in pancreatic cancer progression by modulating CSC properties and chemoresistance through the MIR4435-2HG/miR-1252-5p/STAT1 axis. Targeting MIR4435-2HG presents a promising therapeutic approach to regulate CSCs and improve the efficacy of chemotherapy in pancreatic cancer., Competing Interests: Declarations. Ethics approval and consent to participate: All patients have signed an informed consent form, and the study protocol has acquired official approval from The Tenth Affiliated Hospital of Southern Medical University. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

Noncoding RNA 886 has emerged as a pivotal regulatory RNA with distinct functions across tissues, acting as a regulator of protein activity by directly binding to protein partners. While it is well recognized as a tumor suppressor in prostate cancer, the underlying molecular mechanisms remain elusive. To discover the principal pathways regulated by nc886 in prostate cancer, we used a transcriptomic and proteomic approach analyzing malignant DU145, LNCaP, PC3, and benign RWPE-1 prostate cell line models transiently transfected with in vitro transcribed nc886 or antisense oligonucleotides. Multiomics revelead a significant enrichment of immune system-related pathways across the cell lines, including cytokines and interferon signaling. The interferon response provoked by nc886 was validated by functional assays. The invariability of PKR phosphorylation and NF-κB activity in the gain/loss of nc886 function experiments and the positive regulation of innate immunity suggest a PKR-independent mechanism of nc886 action. Accordingly, the GSEA of the PRAD-TCGA data set revealed immune stimulation as the nc886 most associated node also in the clinical setting. Our study showed that the reduction of nc886 leads to a blunted immune response in prostate cancer.

Background: Pleural Mesothelioma (PM) is a highly aggressive cancer, for which effective early detection remains a challenge due to limited screening options and low sensitivity of biomarkers discovered so far. While extracellular vesicles (EVs) have emerged as promising candidates for blood-based biomarkers, their role in PM has not been studied yet. In this study, we characterized the transcriptomic profile of EVs secreted by PM primary cells and explored their potential as a biomarker source for PM detection., Methods: We collected cell culture supernatant from early-passage PM cell cultures derived from the pleural effusion of 4 PM patients. EVs were isolated from the supernatant using Qiagen exoEasy Maxi kit. RNA isolation from EVs was done using the mirVana PARIS kit. Finally, single-end RNA sequencing was done with Illumina Novaseq 6000., Results: We identified a range of RNA species expressed in EVs secreted by PM cells, including protein-coding RNA (80%), long non-coding RNA (13%), pseudogenes (4.5%), and short non-coding RNA (1.6%). We detected a subset of genes associated with the previously identified epithelioid (32 genes) and sarcomatoid molecular components (36 genes) in PM-EVs. To investigate whether these markers could serve as biomarkers for PM detection in blood, we compared the RNA content of PM-EVs with the cargo of EVs isolated from the plasma of healthy donors (publicly available data). Majority of upregulated genes in PM-EVs were protein-coding and long non-coding RNAs. Interestingly, 25 of them were the sarcomatoid and epithelioid marker genes. Finally, functional analysis revealed that the PM-EV RNA cargo was associated with Epithelial-Mesenchymal transition, glycolysis, and hypoxia., Conclusions: This is the first study to characterize the transcriptomic profile of EVs secreted by PM primary cell cultures, demonstrating their potential as biomarker source for early detection. Further investigation of the functional role of PM-EVs will provide new insights into disease biology and therapeutic avenues., Competing Interests: Declarations. Code availability: R code used to analyze the data have been provided in the Supplementary Files. Ethics approval and consent to participate: All procedures involving pleural mesothelioma primary cultures were approved by the Ethics Committee of the canton Zurich on 09/02/2021 with the approval number BASEC-Nr. 2020–02566. Consent for publication: Not applicable. Competing interests: IO has received institutional grants from Roche and Medtronic, consulting fees from Intuitive, and lecture honoraria from Roche and AstraZeneca. IO has also participated in advisory boards for AstraZeneca, MSD, BMS and Medtronic. The remaining authors declare no competing interests., (© 2025. The Author(s).)

Background: FcγRI, a pivotal cell surface receptor, is implicated in diverse immune responses and is ubiquitously expressed on numerous immune cells. However, its role in intracellular bacterial infections remains understudied., Methods: Wild-type (WT) and FcγRI knockout (FcγRI-KO) mice were inoculated intranasally with a specific dose of C. muridarum. Lung tissues were harvested for transcriptome sequencing, and flow cytometry was employed to validate bioinformatics immune infiltration analysis. Differentially expressed DC-associated genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to elucidate their functions during infection. A PPI network was constructed to pinpoint crucial genes, and qPCR was utilized to confirm their expression changes. Additionally, we compared body weight, lung Chlamydia load, and pathological alterations between WT and FcγRI-KO mice post-infection to assess the effect of FcγRI on inflammation via gene regulation. Lastly, an mRNA-miRNA-lncRNA network was formulated to further probe the molecular mechanisms of FcγRI in C. muridarum infection., Results: Post-C. muridarum infection, FcγRI-KO mice exhibited a notable decrease in DC infiltration and maturation, along with downregulated co-stimulatory molecules (CD40, CD80, CD86) in lung tissues. Differential gene analysis identified 26 differentially expressed DC-related genes implicated in DC proliferation, migration, and inflammatory responses. KEGG analysis revealed their close association with key immune pathways. The PPI network delineated two modules, with the top six genes in the pivotal cluster 1 (Ccl4, Il6, Ccl3, Ptgs2, Il 1α, Il7) being significantly downregulated in FcγRI-KO mice. A ceRNA network encompassing 12 miRNAs and 37 lncRNAs regulating four key genes (Ptgs2, Il1α, Il6, Il7) was also constructed., Conclusions: In C. muridarum respiratory infections, FcγRI facilitates DC infiltration and maturation, upregulates six pro-inflammatory genes (Ccl4, Il6, Ccl3, Ptgs2, Il1α, Il7), and exhibits a pro-inflammatory role. A key ceRNA network was formulated to unravel the underlying molecular mechanisms., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Hypoxia ischemia (HI) injury is an inevitable risk factor in kidney transplantation. The inflammatory response is crucial in HI. Long non-coding RNAs (lncRNAs) are known to regulate inflammation and immunity, but their role in HI remains unclear., Methods: HI gene expression analysis was conducted using Gene Expression Omnibus datasets, followed by experiments on patient tissues and cell lines. Subsequently, loss-of-function assays characterized AC006129.1 in HK2 cells, while RIP, RNA pull-down, and mRNA degradation assays explored its relationship with CXCL2 mRNA. Rescue experiments assessed the impact of these interactions on cell proliferation, apoptosis, and inflammation in vitro. Additionally, ChIP and dual-luciferase reporter assays were conducted to investigate the mechanism behind AC006129.1 upregulation., Results: Among the 469 dysregulated long non-coding RNAs (lncRNAs), AC006129.1 exhibited a significant upregulation in cases of kidney HI. This finding was corroborated in clinical specimens and cell lines. AC006129.1 expression inhibits proliferation, induces apoptosis, and triggers the inflammatory response due to HI. Mechanistically, AC006129.1 facilitated the interaction between CXCL2 mRNA and the RNA-binding protein HuR, thereby stabilizing CXCL2 mRNA. Rescue experiments further demonstrated that AC006129.1 modulated HI injury through its influence on CXCL2. Additionally, ERG1 was found to specifically interact with the promoter region of AC006129.1, thereby activating its transcription., Conclusions: Our findings indicate that AC006129.1 plays a pathogenic role in the HI process by enhancing the inflammatory response, which exacerbates kidney cell damage. This suggests that AC006129.1 is a critical factor in the development of HI and represents a potential diagnostic and therapeutic target., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Despite the availability of various treatment options, glioblastoma (GBM) remains an extremely aggressive form of glioma with a poor prognosis. In recent studies, regulatory cell death (RCD) has been identified as an effective mechanism to suppress glioma. Cuproptosis, caused by intracellular copper, is a novel RCD process that affects chemotherapy efficacy and glioma progression; however, the precise function of cuproptosis-related lncRNAs (CRLs) and cuproptosis-related genes (CRGs) in GBM remains uncertain. To determine whether CRLs and CRGs have prognostic significance, a GBM cohort in TCGA to build a novel cuproptosis-related risk model. Two high-risk CRLs (AC091182.2, AC005229.4) and their co-expression CRGs (LIPT2, GLS) were identified and verified to constitute an independent prognostic indicator of GBM. RT-qPCR analysis confirmed that the high-risk CRLs and CRGs were highly expressed in GBM cells compared to normal astrocytes. By constructing a mouse GBM model, high-risk CRLs and CRGs were found to be expressed at higher levels in tumor tissues. Furthermore, to verify whether these CRLs and CRGs are associated with GBM cuproptosis, cuproptosis cell models were constucted in GBM cell lines and astrocyte by using Elesclomol and CuCl2. It was found that the expression of high-risk CRLs and CRGs was decreased upon cuproptosis-induced in GBM cells. Interestingly, normal astrocytes were less sensitive than GBM cells to cuproptosis-inducing drugs, and the effects of the drugs on the expression of the CRLs and CRGs in normal astrocytes were opposite to that of in GBM cells. In conclusion, by constructing a novel cuproptosis-related risk model, two high-risk CRLs and CRGs were identified. Their specific pointing to GBM has been demonstrated through a variety of experiments. These CRLs and CRGs might serve as prognostic markers and indicators for GBM and provide theoretical support for future GBM treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Long non-coding RNAs (lncRNAs) have emerged as essential regulators of gene expression, significantly influencing various biological processes. Approximately half of all lncRNAs are classified as long intergenic non-coding RNAs (lincRNAs), which are situated among coding genes. Recent studies have documented the role of lincRNAs in the pathogenesis of lung diseases, including lung cancer, pulmonary fibrosis, and pulmonary arterial hypertension. These lincRNAs can modulate gene expression through various mechanisms, including epigenetic modifications, transcriptional regulation, and post-transcriptional regulation. By functioning as competing endogenous RNAs (ceRNAs), lincRNAs can affect the activity of microRNAs (miRNAs) and their corresponding target genes. This review delves into the intricate mechanisms by which lincRNAs contribute to the development and progression of various lung diseases. Furthermore, it discusses the potential of lincRNAs as therapeutic targets., Competing Interests: Declarations. Ethics approval and consent to participate: Not Applicable. Consent for publication: Not applicable. Human and animal ethics: Not applicable. Conflict of interest: The authors declare no competing interests. Clinical trial number: Not Applicable., (© 2025. The Author(s).)

Long non-coding RNAs (lncRNAs) are long RNA transcripts with length >200 nucleotides that do not encode proteins. They play a crucial role in regulating HIV-1 infection, yet their involvement in myeloid cells remains underexplored. Myeloid cells are susceptible to HIV infection and contribute substantially to the latent HIV reservoir. Therefore, disruption of latency within these reservoirs is crucial for achieving a definite cure. In this study, we aimed to ascertain the role of MALAT1 lncRNA in reversal of HIV-1 latency. Latently HIV-infected cell line, U1 was treated with SAHA, followed by qRT-PCR assays to confirm HIV-1 reactivation, and MALAT1 expression was assessed. The in vitro experiments revealed a significant increase in MALAT1 expression following latency reactivation and HIV-1 infection, while its knockdown using siRNA resulted in suppression of HIV transcription, which implies that MALAT1 play a significant role in facilitating the reversal of HIV-1 latency by promoting HIV transcription. Clinical samples were analysed to measure MALAT1 and pro-inflammatory cytokines expression. The elevated MALAT1 expression in treatment-naïve subjects compared to those on ART and HIV-negative controls suggests its association with HIV replication. Moreover, correlation analysis revealed a positive association between MALAT1 expression and pro-inflammatory cytokines, TNF-α and IP-10. To conclude, MALAT1 lncRNA emerged as a crucial facilitator of HIV-1 latency reversal in latently infected monocytes by inducing the expression of pro-inflammatory factors. These findings highlight that MALAT1 could potentially be explored as the therapeutic intervention to reactivate latent cells in monocytes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Emerging evidence has indicated that m5C modification plays a vital role in cancer development. However, the function of m5C-lncRNAs in PTC has never been reported. This study aims to explore the regulation mechanism of m5C RNA methylation-related long noncoding RNAs (m5C-lncRNAs) in papillary thyroid cancer (PTC). Bioinformatics analysis was used to investigate the role of m5C-lncRNAs in the prognosis and tumor immune microenvironment of PTC. Subsequently, we preliminarily verified the regulation mechanisms of m5C-lncRNAs in vivo and in vitro experiments. A total of six m5C-lncRNAs and five immune cell types were selected to construct the risk score and immune risk score (IRS) model, respectively. Patients with a high-risk score had a worse prognosis and the ROC indicated a reliable prediction performance (AUC = 0.796). As expected, the ESTIMATE and immune scores were higher (P < 0.001) and the tumor purity (P < 0.05) was significantly lower in the low-risk subgroup. CIBERSORT analysis showed Tregs, M0 macrophages, dendritic cells resting, and eosinophils were positively correlated to the risk score. Moreover, the expression levels of PD-1, PD-L1, CTLA-4, TIM-3, LAG-3, and KLRB1 were lower in the high-risk subgroup. Importantly, patients in high-risk subgroup tended to have a better response to immunotherapy than those in low-risk subgroup (P = 0.022). Similar to the above risk score, the IRS model also showed favorable prognosis predictive performance (AUC = 0.764). An integrated nomogram combining risk score, IRS, and age exhibited good prognostic predictive performance. Additionally, we validate the downregulation of PPP1R12A-AS1 promotes proliferation and metastasis by activating the MAPK signaling pathway. Our research confirms that m5C-lncRNAs not only contribute to evaluating the prognosis of patients with PTC but also help predict immune cell infiltration and immunotherapy response., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Informed consent was obtained from all the participants and approved by the Ethics Committee of Xiangya Hospital of Central South University (No. 202004192)., (© 2025. The Author(s).)

Long non-coding RNA rhabdomyosarcoma 2-associated transcript (RMST) is a crucial regulator in various biological processes, particularly in neurogenesis and cancer progression. This review summarizes current knowledge on structure, expression patterns and functional roles across different organs and diseases of RMST. RMST exhibits tissue-specific expression, notably in brain tissues and vascular endothelial cells, and plays a significant role in neuronal differentiation through interaction with SRY-box 2. In cancer, RMST predominantly functions as a tumour suppressor, with context-dependent roles observed across different cancer types. RMST is also implicated in neurological disorders, cardiovascular diseases and Hirschsprung's disease. Mechanistically, RMST acts as a competing endogenous RNA and a transcriptional regulator, interacting with various microRNAs and proteins to modulate gene expression. The potential of RMST as a biomarker and therapeutic target is increasingly recognized, particularly in atherosclerosis and cancer. While current findings are promising, further research is needed to fully elucidate the functions and translate these insights into clinical applications of RMST. This review underscores the significance of RMST in cellular processes and disease pathogenesis, highlighting its potential as a novel target for diagnostic and therapeutic interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.)

Background and Aims: The intima-media thickness (IMT) of the carotid artery, an indicator of subclinical atherosclerosis, varies in close association with various factors such as diabetes and immune response. The extent of changes in IMT varies among individuals owing to both genetic and epigenetic factors. In this study, we aimed to identify single nucleotide polymorphisms (SNPs) and DNA methylation patterns that affect carotid IMT in monozygotic (MZ) twins., Methods: We measured the maximum IMT (IMT-Cmax) and the mean IMT in the common carotid artery wall using ultrasonography in 107 pairs of MZ twins recruited from the Osaka University Twin Registry. The genotyping of SNPs and the measurement of methylation levels were performed using a beads array, and the expression of each gene was determined by RNA sequencing. Linear regression analysis was performed on each of the two groups: one group consisted of twins randomly selected from each pair, and the other group consisted of co-twins., Results: We identified a CpG site (cg02432467) on HS3ST6 as a significant epigenetic factor in both IMT-Cmax and mean IMT analyses. The methylation level at another site (cg07927379) was negatively correlated with LINC01006 expression and IMT-Cmax. Furthermore, there were significant differences in AP2A2 expression and mean IMT among individuals with each genotype of the rs10902263 polymorphism., Conclusions: We identified genetic and epigenetic factors associated with carotid IMT that may be useful for individualized assessments., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Mikio Watanabe reports financial support was provided by Japan Society for the Promotion of Science. Osaka Twin Research Group reports financial support was provided by Government of Japan Ministry of Education Culture Sports Science and Technology. Osaka Twin Research Group reports equipment, drugs, or supplies was provided by Beckman Coulter Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the effects of long non-coding RNA KLHL7-AS1 (LncRNA KLHL7-AS1) on the proliferation and apoptosis of nucleus pulposus cells under oxidative stress and its mechanisms. Methods: Human nucleus pulposus cells (HUM-iCell-s012) were divided into 4 groups, and unoxidized nucleus pulposus cells were transfected with an empty pcDNA vector (pcDNA-control) to serve as the blank control group. Based on previous studies on oxidative stress-induced nucleus pulposus cell senescence and preliminary experiments, oxidative stress was induced by treating nucleus pulposus cells with 400 μmol/L H 2 O 2 . Oxidized nucleus pulposus cells were transfected with pcDNA-control, KLHL7-AS1 interfering RNA (siRNA-KLHL7-AS1), or KLHL7-AS1 overexpression plasmid (pcDNA-KLHL7-AS1), forming the model control group (H 2 O 2 +pcDNA-control), the model silencing group (H 2 O 2 +siRNA-KLHL7-AS1), and the model overexpression group (H 2 O 2 +pcDNA-KLHL7-AS1), respectively. Following these treatments, KLHL7-AS1 expression levels, cell proliferation, cell apoptosis were measured and compared among the groups, and the expression levels of B-cell lymphoma 2 (BCL-2) and BCL-2-associated X protein (BAX) in the groups of cells were compared too ( n =3). Results: The expression of KLHL7-AS1 in the model control group was significantly higher than that in the blank control group (7.716±0.851 vs 0.996±0.086, P <0.001). Furthermore, the expression of KLHL7-AS1 in the model overexpression group was markedly higher than that in the model silencing group (19.592±1.747 vs 4.222±0.039, P <0.001). Compared to the blank control group, the model silencing group showed no significant change in cell viability (0.125±0.006 vs 0.127±0.010, P =0.390), an increased apoptosis rate (17.2%±1.7% vs 11.5%±1.0%, P <0.05), elevated BCL-2 protein expression (0.897±0.025 vs 0.730±0.026, P <0.05), and reduced BAX protein expression (0.250±0.030 vs 0.523±0.015, P <0.05). In comparison to the model control group, the model silencing group exhibited increased cell viability (0.125±0.006 vs 0.076±0.008), reduced apoptosis rates (17.2%±1.7% vs 30.7%±2.3%), elevated BCL-2 protein expression (0.730±0.026 vs 0.440±0.036), and decreased BAX protein expression (0.523±0.015 vs 0.723±0.021) (all P <0.001). In comparison to the model silencing group, the model overexpression group showed reduced cell viability (0.125±0.006 vs 0.039±0.006), increased apoptosis rates (43.1%±1.9% vs 17.2%±1.7%), decreased BCL-2 protein expression (0.227±0.021 vs 0.730±0.026), and increased BAX protein expression (1.147±0.035 vs 0.523±0.015) (all P <0.001). Conclusions: Downregulation of KLHL7-AS1 expression promotes the proliferation of nucleus pulposus cells and inhibits their apoptosis, it may involve the regulation of BCL-2 and BAX protein synthesis, potentially delays the progression of intervertebral disc degeneration.

Neospora caninum is one of the most common pathogens causing reproductive failure in ruminants (e.g., cattle and goats) worldwide. However, due to a poor understanding of the pathogenic mechanisms of N. caninum infection, no effective drugs and vaccines are currently available. Long non-coding RNAs (lncRNAs) have been reported to be important regulators involved in a great number of physiological and pathological processes. Our previous study found that N. caninum infection induced significantly aberrant expression of lncRNA profiles in caprine endometrial epithelial cells (EECs). In the present study, we found that N. caninum infection specifically suppressed the expression of a novel lncRNA, XR&#95;001919077.1 , and knockdown of XR&#95;001919077.1 with small interfering RNA significantly promoted the propagation of N. caninum in caprine EECs. Rapid amplification of cDNA ends analysis generated six splice variants of XR&#95;001919077.1 , with lengths ranging from 592 to 694 nt. Transfection of the full length of each variant markedly inhibited the propagation of N. caninum in caprine EECs. Further study suggested that XR&#95;001919077.1 acted as a sponge of Chi-miR-93-5p to promote the expression of sirt1 , and the XR&#95;001919077.1 /Chi-miR-93-5p/ sirt1 axis significantly delayed the in vitro growth of N. caninum in caprine EECs by regulating host cell mitochondrial function and autophagy. Our findings provide a novel insight to understand the interactions between N. caninum and host cells.IMPORTANCEThe uterus is an indispensable reproductive organ for embryo implantation and fetal growth. The endometrium is more vulnerable to infection by pathogenic microorganisms resulting in an increased risk of miscarriage. Neospora caninum is one of the most common pathogens causing miscarriage in ruminants and is able to naturally inhabit the uterus, with N. caninum tissue cysts found in the endometrium. Recent advances in N. caninum research have revealed aberrant expression of long non-coding RNA (lncRNA) profiles in infected caprine endometrial epithelial cells. In the present study, N. caninum , but not Toxoplasma gondii, which has similar morphological and biological features to N. caninum , specifically suppresses the expression of a host lncRNA, XR&#95; 001919077.1 , to impair host's defense through the competitive endogenous RNA mechanism to modulate the host cell mitochondrial function and autophagy to facilitate parasite propagation. The findings suggest a novel immune evasion strategy of N. caninum to facilitate intracellular propagation and provide an alternative path to develop control strategies against neosporosis., Competing Interests: The authors declare no conflict of interest.

Background: Paratuberculosis (Johne's disease, JD) is a chronic and enteric disease in a range of ruminants, often caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection, leading to substantial economic losses worldwide. Yet, the molecular underpinning of paratuberculosis remains elusive. Here we performed RNA sequencing (RNA-seq) and small RNA sequencing (sRNA-seq) of the jejunum tissues from the Holstein cows with three distinct statuses of paratuberculosis, i.e., healthy, subclinical, and clinical to screen potential genes, lncRNAs, and miRNAs associated with the resistance or susceptibility to MAP infection and build ceRNA regulatory networks via miRNAs., Results: We applied whole transcriptome sequencing analysis to examine the jejunum tissue in nine Holstein cows. Starting with 19,994 expressed genes, 13,529 lncRNAs, and 735 miRNAs, we screened out differentially expressed genes (DEGs), lncRNAs, and miRNAs of three comparison groups, i.e., clinical vs. healthy, subclinical vs. healthy, and clinical vs. subclinical, subsequently identifying ceRNA pairs. Ultimately, we detected 76, 74, and 24 DEGs, 19, 39, and 10 lncRNAs, as well as 28, 61, and 20 miRNAs across the three comparison groups, respectively. Through integrating these DEGs with functional annotation, previously reported QTLs, and GWAS results, we proposed eight genes (LYZ, LYZ1, BOLA-DQB, BOLA-DQA1, TAP, CATD, VNN1, and PPARG), six lncRNAs, 48 miRNAs, and 107 ceRNA pairs implying their potential associations with susceptibility to MAP infection., Conclusion: The present study provided a global view of the dynamics in transcriptomes of the bovine jejunum tissues in terms of JD status. Our results demonstrated that not only mRNAs but also lncRNAs and miRNAs played important roles in regulating MAP infection in dairy cattle. This study provided a valuable resource for understanding the molecular basis of JD, potentially contributing to the genetic improvement of JD resistance in dairy cattle., Competing Interests: Declarations. Ethics approval and consent to participate: All protocols for the collection of the blood and hair samples of Chinese Holstein cows were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at China Agricultural University. Blood and hair samples were collected specifically for this study following standard procedures with the full agreement of the Beijing Dairy Cattle Center who owned the animals. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

N 6 -methyladenosine (m 6 A) has emerged as the most prevalent form of RNA modification found across various RNA classes. The detection and quantification of m 6 A RNA modifications under various physiological conditions are crucial for elucidating disease mechanisms and identifying potential therapeutic targets. However, visualizing intracellular m 6 A modifications at single-base resolution remains a significant challenge. Existing methods based on high-throughput sequencing or in vitro assays are not suitable for in situ m 6 A RNA imaging. In this work, we introduce the TadA8.20-assisted N 6 -methyladenosine RNA imaging at single-base resolution (TARS) method for precise visualization and quantification of both A and m 6 A forms at specific RNA sites within single cells. Validation studies using TARS on MALAT1 lncRNA in HeLa cells and CCND1 mRNA in breast cancer cell lines demonstrated its high specificity and efficiency in mapping and quantifying m 6 A modifications at single-base resolution. TARS represents a novel tool that advances m 6 A RNA modification research by offering accurate and detailed insights into m 6 A modifications at the single-base level., (© 2024 Wiley-VCH GmbH.)

The leading form of cancer affecting females globally is breast cancer, characterized by an unregulated growth of cells within the breast. Therefore, examining breast tissue is crucial in accurately identifying and treating this disease. Exosomes are very small enclosures bounded by a layer of cells and produced by a variety of cells present in the cancerous tissue surroundings. They play a crucial role in several biological functions in cancerous tumors. These exosomes carry non-coding RNAs (ncRNAs) and are discharged into the TME, where they are instrumental in the development and advancement of tumors. Additionally, the ncRNAs enclosed in exosomes act as significant mediators of communication within cells. Consequently, there is limited comprehension regarding the precise roles and targets of exosomal RNA in regulation, as research in this area is still in its preliminary phases. This piece provides a comprehensive overview of the latest studies on exosomes, delving into their impact on the behavior of cancer cells and immune cells. Moreover, it presents a compilation of the diverse forms of non-coding RNA molecules found in exosomes released by both cancerous and supportive cells, including circular RNAs, microRNAs, and long non-coding RNAs. Current research has proven the noteworthy influence that non-coding RNA molecules have on the progression, proliferation, drug resistance, and immune responses of breast cancer cells., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chemotherapy is an effective treatment for gastric cancer. However, many patients develop resistance to chemotherapeutic agents during clinical treatment. LncRNA CCAT1 has recently been shown to influence cellular resistance to specific chemotherapeutic drugs, but its role in gastric cancer remains underexplored. This study aims to investigate the role of LncRNA CCAT1 in cisplatin resistance in gastric cancer cells and its potential underlying mechanisms. Gastric cancer cell lines with acquired resistance were established. The expression of CCAT1 was assessed in both cisplatin-sensitive and cisplatin-resistant AGS cell lines. CCAT1 expression was knocked down in AGS/DDP cells, and the changes in IC50 values were measured using the Cell Counting Kit-8 (CCK-8) assay. Apoptosis in gastric cancer cells was evaluated by flow cytometry. Additionally, Western blotting was employed to measure the expression levels of PI3K/AKT/mTOR signaling pathway proteins and apoptosis-related proteins in both interference and control groups. RT-qPCR results indicated that CCAT1 expression was significantly elevated in cisplatin-resistant gastric cancer cells compared to non-resistant cells. Similarly, CCK-8 assay results demonstrated that knocking down CCAT1 in resistant cells increased their sensitivity to cisplatin treatment. Flow cytometry and Western blot results further confirmed that silencing CCAT1 promoted apoptosis in these cells. Additionally, the expression of PI3K/AKT/mTOR signaling pathway proteins was higher in resistant cells compared to their sensitive counterparts, and silencing CCAT1 in AGS/DDP cells resulted in reduced expression of these proteins. In conclusion, the above studies demonstrated that LncRNA CCAT1 induced cisplatin resistance in gastric cancer cells., (© 2025 Wiley Periodicals LLC.)

Acquired resistance poses a significant obstacle to the effectiveness of platinum-based treatment for cancers. As the most abundant antioxidant, glutathione (GSH) enables cancer cell survival and chemoresistance, by scavenging excessive reactive oxygen species (ROS) induced by platinum. Therapeutic strategy targeting GSH synthesis has been developed, however, failed to produce desirable effects in preventing cancer progression. Thus, uncovering mechanisms of rewired GSH metabolism may aid in the development of additional therapeutic strategies to overcome or delay resistance. Here, we identify upregulation of long noncoding RNA (lncRNA) GDIL (GSH Degradation Inhibiting LncRNA) in platinum resistant colorectal cancer (CRC) and ovarian cancer cells compared with parental ones. High expression of GDIL in resistant CRC is associated with poor survival and hyposensitivity to chemotherapy. We demonstrate that GDIL boosted GSH levels and enhances clearance of ROS induced by platinum. Metabolomic and metabolic flux analysis further reveals that GDIL promotes GSH accumulation by inhibiting GSH degradation. This is attributed by downregulation of CHAC1, an enzyme that specifically degrades intracellular GSH. Mechanistically, GDIL binds and re-localizes the nuclear protein XRN2 to the cytoplasm, where GDIL further serve as a scaffold for XRN2 to identify and degrade CHAC1 mRNA. Suppression of GDIL with selective antisense oligonucleotide, restored drug sensitivity in platinum resistant cell lines and delayed drug resistance in cell line- and patient-derived xenografts. Thus, lncRNA GDIL is a novel target to promote GSH degradation and augment platinum therapy., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Written informed consent for using tumor tissues and clinical data in this study was obtained from each patient from Huashan Hospital and this research was approved by the Ethics Committee of Fudan University (approval number: 2020-578, date: 2020-03-31). All the research was carried out in accordance with the provisions of the Helsinki Declaration of 1975. In vivo experiments in this study complied with the ARRIVE guidelines and were conducted in accordance with the National Research Council’s Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee at Fudan University., (© 2025. The Author(s).)

Despite the advancements and release of new therapeutics in the past few years, cardiovascular diseases (CVDs) have remained the number one cause of death worldwide. Genetic variation of a 9p21.3 genomic locus has been identified as the most significant and robust genetic CVD risk marker on the population level, with the strongest association with coronary artery disease (CAD) and other diseases, including diabetes and cancer. Several mechanisms of 9p21.3 in CVDs have been proposed, but their effects on CVDs have remained elusive. Moreover, most of the single nucleotide polymorphisms (SNPs) associated with CAD are located on a sequence of a long noncoding RNA (lncRNA) called ANRIL . ANRIL has several linear and circular splicing isoforms, which seem to have different effects and implications for CVDs. The mechanisms of the 9p21.3 locus and the interplay of its coding and noncoding transcripts in different diseases require further research. Circular RNAs have generally raised interest due to their beneficial features as biomarkers and therapeutic molecules. Here, we review the literature of 9p21.3 from its identification in 2007 and draw the current knowledge on its function, implications in CVDs, and therapeutic potential.

Retinal detachment (RD) is the separation of the neural retina from the retinal pigment epithelium, with photoreceptor degeneration being a major cause of irreversible vision loss. Herein, ischemia and hypoxia after RD decreased the level of miR-7a-5p (miR-7) and promoted the expression of its main target, α-synuclein (α-syn), which activated the parthanatos pathway and led to photoreceptor damage. Circular RNA CDR1as is an antisense transcript of cerebellar degeneration-associated protein 1, which functions as a "sponge" for miR-7, thereby regulating the abundance and activity of miR-7. In this study, CDR1as expression was elevated after RD. Adeno-associated virus serotype 9 vector containing the shRNA-CDR1as sequence was used to inhibit CDR1as expression via subretinal injection. Hematoxylin and eosin staining and transmission electron microscopy revealed that the morphology and outer nuclear layer thickness of the retina were preserved and photoreceptor cell death was decreased after experimental RD in mice. Mechanistically, CDR1as deficiency significantly increased the expression of miR-7, then decreased the expression of α-syn, poly (ADP-ribose) polymerase 1, apoptosis-inducing factor, and migration inhibitory factor. Furthermore, visual function was improved as shown by Morris water maze experiments in the mouse model of RD. These findings suggest a surprisingly neuroprotective role for CDR1as deficiency, which is probably mediated by enhancing miR-7 activity and inhibiting α-syn/poly (ADP-ribose) polymerase 1/apoptosis-inducing factor pathway, thereby preventing photoreceptor degeneration., Competing Interests: Disclosure Statement None declared., (Copyright © 2025 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Intraventricular hemorrhage results in posthemorrhagic hydrocephalus (PHH). Neonatal hydrocephalus remains a challenging disease due to the high failure rate of all management strategies. We evaluated long noncoding RNA growth arrest-specific 5 (GAS5)-mediated network in neonatal hydrocephalus, providing a new direction for the treatment of hydrocephalus. The PHH model was constructed in neonatal rats after intracerebroventricular injection with GAS5, miR-325-3p, and chaperonin containing T-complex protein 1, subunit 8 (CCT8) plasmids, or oligonucleotides. Next, behavioral tests, measurement of serum inflammation, observation of brain tissue pathology, and calculation of hemoglobin and brain water contents were implemented. GAS5, miR-325-3p, and CCT8 expression, in combination with their interactions, was checked. As the results reported, collagenase infusion induced hydrocephalus, impairing neurological function, enhancing inflammation and neuronal apoptosis, and increasing hemoglobin and brain water contents. GAS5 and CCT8 were up-regulated, while miR-325-3p was down-regulated in hydrocephalic rats. Downregulating GAS5/CCT8 or upregulating miR-325-3p could inhibit inflammatory response and improve neurological function in young hydrocephalic rats. GAS5 promotes CCT8 expression through sponge adsorption of miR-325-3p. GAS5 silencing-mediated protections against hydrocephalus were counteracted by CCT8 overexpression. In summary, GAS5 aggravates neonatal hydrocephalus and inflammatory responses in a way of leasing miR-325-3p-involved regulation of CCT8., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest to declare. Ethical Approval: All animal experiments were complied with the ARRIVE guidelines and performed in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. The experiments were approved by the Institutional Animal Care and Use Committee of Chongqing Medical University (Approval Number: 201706-AC59311)., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

Long noncoding RNA (lncRNA) are essential for modulating the onset and progression of alcohol use disorder (AUD). In this study, we investigated the molecular pathways through which lncRNA may contribute to AUD development. We assessed the expression levels of long noncoding RNA GAS5 (lncRNA GAS5) and microRNA-136-5p (miR-136-5p) in AUD tissue samples and cell lines using reverse transcription-quantitative polymerase chain reaction. Detection of GAS5 N6-methyladenosine (m6A) modifications, facilitated by alkylation repair homolog 5 (ALKBH5), was performed using RNA immunoprecipitation and RNA pull-down assays. The effect of GAS5 on the functionality of SH-SY5Y cells was evaluated using CCK-8 and Transwell assays. Our findings showed high levels of GAS5 expression in both AUD tissues and cell lines. Overexpression of GAS5 decreased the migratory capability of SH-SY5Y cells, whereas silencing GAS5 increased this ability. Bioinformatics analyses predicted a relationship between expression levels of miR-136-5p and GAS5, which was subsequently confirmed using dual-luciferase reporter assays. Additionally, we discovered that GAS5 acts as a sponge for miR-136-5p, leading to the upregulation of ATF2. Elevated levels of ATF2 are associated with M1 microglial polarization. In summary, m6A-modified GAS5 may influence the M1 polarization of microglia via the miR-136-5p/ATF2 pathway. Statistical evaluations were performed using GraphPad Prism V8.0, employing the student's t-test for comparisons between two groups, assuming a normal distribution and equal variances. When variances were unequal, but normality was maintained, the corrected Student's t-test was applied. The non-parametric Wilcoxon rank-sum test was used to analyze non-normally distributed data, and one-way ANOVA was used to compare three or more groups. Independent replication was ensured in the studies, with each experiment repeated at least three times and statistical significance was set at P < 0.05., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Numerous studies over the past few decades have shown that RNAs are multifaceted, multifunctional regulators of most cellular processes, contrary to the initial belief that they only act as mediators for translating DNA into proteins. LncRNAs, which refer to transcripts longer than 200nt and lack the ability to code for proteins, have recently been identified as central regulators of a variety of biochemical and cellular processes, particularly cancer. When they are abnormally expressed, they are closely associated with tumor occurrence, metastasis, and tumor staging. Therefore, through searches on Google Scholar, PubMed, and CNKI, we identified five five recently characterized lncRNAs-Lnc-SLC2A12-10:1, LncRNA BCRT1, lncRNA IGFBP4-1, LncRNA PCNAP1, and LncRNA CDC6-that have been linked to the promotion of cancer cell proliferation, invasion, and metastasis. Consequently, this review encapsulates the existing research and molecular underpinnings of these five newly identified lncRNAs across various types of cancer. It suggests that these novel lncRNAs hold potential as independent biomarkers for clinical diagnosis and prognosis, as well as candidates for therapeutic intervention. In parallel, we discuss the challenges inherent in the research on these five newly discovered lncRNAs and look forward to the avenues for future exploration in this field., Competing Interests: Declarations. Conflict of interest: The authors have no conflict of interest. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent: Not applicable., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Objective: To investigate the mechanism of serum exosomes in chronic obstructive pulmonary disease (COPD), especially the effect of lncRNA TBX2-AS1 on macrophage polarization., Methods: Screen differentially expressed genes through bioinformatics analysis, detect the expression of related molecules in clinical samples and cell experiments, construct a mouse model and conduct functional rescue experiments, using various experimental techniques such as RT - qPCR, Western Blot, flow cytometry, ELISA, and luciferase reporter assay., Results: TBX2-AS1 is highly expressed in the serum and serum exosomes of COPD patients, and it can promote macrophage M1 polarization and inhibit M2 polarization; it exerts its role by negatively regulating the miR-423-5p/miR-23b - 3p axis, where miR-423-5p inhibits CELSR2 expression to prevent M1 polarization, and miR-23b-3p inhibits NEK6 expression to promote M2 polarization; in vivo experiments, down-regulation of CELSR2/NEK6 can reverse the promoting effect of COPD serum exosomes on lung injury and inflammation., Conclusion: COPD serum exosomes deliver TBX2-AS1 to macrophages, regulate the miR-423-5p-CELSR2/miR-23b-3p-NEK6 pathway, affect macrophage polarization, and exacerbate the progression of COPD, providing new directions and potential targets for the diagnosis and treatment of COPD.

Background: The pathogenesis of biliary atresia (BA) remains elusive. We aimed to investigate the role of long noncoding RNA (lncRNA) MEG9 in BA., Methods: LncRNA microarray was conducted to identify differentially expressed lncRNAs in three BA and three para-hepatoblastoma liver tissues. RT-qPCR validated the results. Human intrahepatic bile duct epithelial cells (HIBECs) were stably transfected with lncRNA MEG9 knockdown/overexpression to investigate its cellular localization and function. RNA sequencing (RNA-seq), differentially expressed genes (DEGs) analysis and gene set enrichment analysis were applied to MEG9-overexpresed HIBECs. RNA pull-down and mass spectrometry explored the interacting protein of MEG9, while clinical information was reviewed., Results: 436 differentially expressed lncRNAs were identified, with MEG9 highly upregulated in BA. RT-qPCR further confirmed MEG9's overexpression in BA and diagnostic potential (AUC = 0.9691). MEG9 was predominantly located in the nucleus and significantly promoted cell proliferation and migration. RNA-seq revealed inflammation- and extracellular matrix-related pathways enriched in MEG9-overexpressing HIBECs, with upregulated cytokine genes like CXCL6 and IL6. MMP-7 and collagen I were also overexpressed. Furthermore, 38 proteins were identified to specifically interact with MEG9, and S100A9 was highly expressed in cell models. S100A9 was also significantly upregulated in BA liver tissue and correlated with MEG9 expression (r = 0.313, p < 0.05), albumin level (r = -0.349, p < 0.05), and platelet level (r = -0.324, p < 0.05)., Conclusion: MEG9 influences cholangiocyte proliferation, migration, and cytokine production, potentially regulating BA inflammation and fibrosis via S100A9 interaction., Competing Interests: Conflicts of interest The authors have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Previously considered junk or non-functional, long non-coding RNAs (lncRNAs) have emerged over the past few decades as pivotal components in both physiological and pathological processes, including cancer. Neuroblastoma-associated transcript-1 (NBAT-1) was initially discovered a decade ago as a risk-associated tumor suppressor lncRNA in neuroblastoma (NB). Subsequent studies have consistently demonstrated that NBAT-1 serves as a dedicated tumor suppressor in many cancers. NBAT-1 is significantly downregulated in cancer, which is closely linked to higher histological grades, increased metastasis, and poor survival in cancer patients suggesting NBAT-1's potential as a prognostic biomarker. In this review, we delve into the current body of literature, elucidating the tumor-suppressive roles of NBAT-1 and the underlying regulatory mechanisms in the context of human malignancies. Additionally, we shed light on the mechanisms contributing to the diminished expression of NBAT-1 and its potential as both a prognostic biomarker and a promising therapeutic target in cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent emerging evidence demonstrates that some long non-coding RNAs (lncRNAs) can indeed be translated into functional polypeptides. These discoveries are pivotal for understanding de novo gene birth, the process by which new genes evolve from previously non-genic regions. In this review, we first introduce key methods, such as Ribo-seq and translation initiation site detection by translation complex analysis, for identifying coding sequences within lncRNAs and highlight examples of functional polypeptides derived from lncRNAs across species. These polypeptides play essential roles in maintaining cellular homeostasis and contribute to pathological processes, including cancer. However, because not all lncRNA-derived polypeptides appear to be functional, these lncRNAs may act as gene reservoirs. We also discuss how lncRNAs change their intracellular localization, how lncRNA-derived polypeptides evade immune surveillance, and how they gradually evolve into typical coding RNAs, providing evidence for the evolutionary model of de novo gene birth., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Breast cancer (BC) is the most common malignant tumor in women, and the majority of BC-related deaths are due to tumor metastasis. There is emerging evidence for the role of long noncoding RNAs (lncRNAs) in tumor progression. Nevertheless, lncRNAs that drive metastasis in patients with BC and the underlying mechanisms of lncRNAs are still largely elusive. In this study, we showed that LINC00882 was highly expressed in metastatic BC tissues, and a receiver operating characteristic (ROC) curve was able to distinguish well between BC cases with lymph node metastasis (LNM) and those without LNM. Functionally, LINC00882 promoted BC invasion and metastasis in vitro and in vivo. Mechanistically, at the transcriptional level, CEBP-β could bind directly to the LINC00882 promoter region and activate its transcription. Moreover, at the posttranscriptional level, m 6 A modification of LINC00882 mediated by methyltransferase-like 14 (METTL14) promoted its expression via an IGF2BP2-dependent pathway. Furthermore, 514-615 nucleotides of LINC00882 could directly interact with poly (A) binding protein cytoplasmic 1 (PABPC1) and promote the interaction between PABPC1 and ELK3 mRNA, thereby stabilizing ELK3 mRNA and enhancing the ELK3 protein level. E-cadherin expression was suppressed via ELK3-mediated transcription inhibition, subsequently activating epithelial-mesenchymal transition to promote BC metastasis. These results highlight the role of LINC00882 in BC, and LINC00882 may be a diagnostic and therapeutic target for BC., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Fresh BC tissues were obtained with informed patient consent and approval from the Qilu Hospital of Shandong University, and the Research Ethics Committee of Shandong University. Patients’ privacy has been fully protected. Animal experiments were conducted according to the Guidelines for Animal Health and Use (Ministry of Science and Technology, China, 2006), and were approved by the Committee for Animal Protection of Shandong University. Consent for publication: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Metastasis is the major cause of breast cancer mortality, with angiogenesis and tumor-released exosomes playing key roles. However, the communication between breast cancer cells and endothelial cells and its role in tumor metastasis remains unclear. Here, we characterize a long noncoding RNA, RPPH1, which is upregulated in breast cancer tissues and positively associated with poor prognosis. Hypoxia microenvironment upregulates the expression of RPPH1 in breast cancer cells, and promotes its packaging into exosomes through hnRNPA1, leading to the maintenance of stemness and aggressive traits in cancer cells and angiogenesis in endothelial cells. The function of cellular and exosomal RPPH1 was confirmed in the MMTV-PyMT mouse model, in which ASO-RPPH1 therapy effectively inhibited tumor progression and metastasis. Mechanistically, RPPH1 protects IGF2BP2 from ubiquitination-induced degradation, stabilizes N6-methyladenosine (m6A)-modified FGFR2 mRNA, and activates the PI3K/AKT pathway. Our research unveils the role of RPPH1 in breast cancer metastasis and highlights its potential as a therapeutic target., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Ethical approval was given by the Medical Research Ethics Committee of Nanjing Drum Tower Hospital (Nanjing, China, ethics approval number: 2023-354-01) and written informed consent was obtained from each patient. Animal studies were approved by the animal ethics committee of China Pharmaceutical University (Permit Number: 2162326) and were in accordance with the international laws and policies (EEC Council Directive 86/609,1987)., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Long non-coding RNAs (lncRNAs), serving as diverse functional regulators, are abundantly expressed in the testis. However, many testis-specific or preferentially expressed lncRNAs remain uncharacterized. Here, we report a testis-specific lncRNA, 1700052I22Rik, which exhibits a dynamic expression pattern during spermatogenesis. Our findings demonstrate that knockout of 1700052I22Rik in mice leads to reduced sperm counts and subfertility in males, as well as defective spermatid chromatin condensation. We further elucidate the underlying mechanism by which 1700052I22Rik modulates the translation of protamine 1 (PRM1) through interaction with Y-box binding protein 2 (YBX2). Collectively, our results uncover a crucial role for the testis-specific lncRNA 1700052I22Rik in regulating spermatid chromatin condensation in mice, providing novel insights into the functions of lncRNAs in spermatogenesis and potential targets for the diagnosis and treatment of male infertility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Long noncoding RNAs (lncRNAs) are involved in the host antiviral response, but how host lncRNAs interact with viral proteins remains unclear. The NS1 protein of avian influenza viruses can affect the interferon-dependent expression of several host lncRNAs, but the exact mechanism is unknown. To further investigate the molecular mechanism and functions of NS1 proteins and host lncRNAs, we performed RNA-immunoprecipitation sequencing assays on A549 cells transfected with the H5N1-NS1 gene. We identified multiple sets of host lncRNAs that interact with NS1. The results of the RNA pulldown assay indicated that PIK3CD-AS2 can directly interact with NS1 in vitro. Immunofluorescence confocal microscopy showed that these proteins were colocalized in the nucleus. Further studies revealed that PIK3CD-AS2 can also inhibit the transcription of NS1, which in turn affects the translation of the NS1 protein. PIK3CD-AS2 overexpression regulates NS1 protein-induced cell cycle arrest and initiates apoptosis. We hope this work will help elucidate the molecular mechanisms associated with NS1 proteins in the study of viral infections to promote the development of potential treatments for patients infected with avian influenza A viruses., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or nonfinancial interests to disclose. Ethical approval: Not applicable., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Small proteins are ubiquitous in all kingdoms of life. MicroProteins, initially characterized as small proteins with protein interaction domains that enable them to interact with larger multidomain proteins, frequently modulate the function of these proteins. The study of these small proteins has contributed to a greater comprehension of protein regulation. In addition to sequence homology, sequence-divergent small proteins have the potential to function as microProtein mimics, binding to structurally related proteins. Moreover, a multitude of other small proteins encoded by short open reading frames (sORFs) and peptides, derived from diverse sources such as long noncoding RNAs (lncRNAs) and miRNAs, contribute to a variety of biological processes. The potential of small proteins is evident, offering promising avenues for bioengineering that could revolutionize crop performance and reduce reliance on agrochemicals in future agriculture., Competing Interests: Declaration of interests The authors have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Glioblastoma multiforme (GBM), a highly heterogeneous CNS tumor known for its highest incidence rates and poor prognosis has shown limited success in the therapies due to hypoxia-driving immune-suppression in the tumor microenvironment (TME). Emerging evidence highlights the involvement of tumor cell-derived exosomes in tumor-associated microglia polarization via transfer of exosomal onco-proteins and miRNAs. Although the regulatory role of long noncoding RNAs (lncRNAs) in immune signaling are known, its mechanism in microglial polarization via exosomes in GBM still remains poorly understood. In our study, we found that in comparison to the normoxic GBM-derived exosomes lncRNA H19 was significantly upregulated in hypoxic GBM-derived exosomes. Hypoxic GBM-derived exosomes and secretome (conditioned media) caused the reduction in the % phagocytosis of microglia as compared with the control group. Moreover, GBM secretome caused increase in the M2-specific genes (IL10, STAT-3, CD163, CD206) in microglia indicating its polarization to the protumorigenic (M2) phenotype. LncRNA H19 knocked down GBM-secretome treatment in microglia further reduced the STAT-3 expression indicating H19 mediated signaling. Overall, our results suggest the involvement of hypoxic exosomes and lncRNA H19 in microglial polarization and H19 as a potential target., (© 2025 Wiley Periodicals LLC.)

Hundreds of thousands of small open reading frames (smORFs) of less than 100 codons exist in every genome, especially in long noncoding RNAs (lncRNAs) and in the 5' leaders of mRNAs. smORFs are often discarded as nonfunctional, but ribosomal profiling (RiboSeq) reveals that thousands are translated, while characterised smORF functions have risen from anecdotal to identifiable trends: smORFs can either have a cis-noncoding regulatory function (involving low translation of nonfunctional peptides) or full coding function mediated by robustly translated peptides, often having cellular and physiological roles as membrane-associated regulators of canonical proteins. The evolutionary context reveals that many smORFs represent new genes emerging de novo from noncoding sequences. We suggest a mechanism for this process, where cis-noncoding smORF functions provide niches for the subsequent evolution of full peptide functions., Competing Interests: Declaration of interests The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Backgrounds: Recent studies have found Several lncRNAs were proved differential expression in diminished ovarian reserve (DOR) patients, however, the mechanism of DOR caused by lncRNAs is still largely unclear., Methods: High throughput sequencing was performed in ovarian GCs extracted from women with normal ovarian function and women with DOR. Bioinformation analysis was used to analyze the sequencing data and identify the differential expression of lncRNAs. Quantitative RT-PCR (qRT-PCR) was used to verify the sequencing results. Situ fluorescence hybridization (FISH) followed by confocal microscopy and qRT-PCR were used to explore the location and expression of LncRNA-THBS4 in GCs. The significantly enriched signaling pathways of LncRNA-THBS4 were identified by KEGG. The study used RNA interference technology to decipher LncRNA-THBS4 function by silencing LncRNA-THBS4 in GCs. Western blot and qRT-PCR were used to explore the mRNA and protein expressions of key factors of PI3Ks pathway. The pro-apoptotic protein and anti-apoptotic protein were detected by western blot. The proliferation and apoptosis of GCs were detected by MTT assay and Flow cytometry., Results: 197 lncRNAs with significant differences in expression levels were detected between control and DOR group by high throughput sequencing. The study found the expression of LncRNA-THBS4 in GCs was positively correlated with Anti-Mullerian hormone (AMH) (p = 0.0020, r = 0.4742)、antral follicle count (AFC) (p = 0.0007, r = 0.5130)、good embryo rate (p = 0.0006, r = 0.5210), negatively correlated with basal FSH level (p = 0.0007, r = －0.5152). LncRNA-THBS4 was mainly localized in the cytoplasm of GCs. LncRNA-THBS4 silencing could inhibit the PI3Ks pathway; decrease the levels of anti-apoptotic protein, inhibit the proliferation of GCs; increase the levels of apoptosis protein, enhance the apoptosis of GCs., Conclusions: The expression level of lncRNA-THBS4 is correlated with ovarian function indicators and pregnancy outcomes in women. LncRNA-THBS4 may participate in the pathogenesis of DOR by affecting the proliferation and apoptosis of GCs via regulating PI3K/AKT/mTOR signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Long noncoding RNA (lncRNA) PTTG3P has been demonstrated to participate in the development of hepatocellular carcinoma (HCC) by targeting the mRNA PTTG1. The present study aimed to investigate the diagnostic efficacy of serum lncRNA PTTG3P, mRNA PTTG1 and their combination for the diagnosis and prognosis of HCC. A total of 373 participants were enrolled in the present study, including 73 patients with HCC, 100 patients with chronic hepatitis B (CHB), 100 patients with liver cirrhosis (LC) and 100 healthy controls (HCs). The expression levels of serum RNAs were quantified by reverse transcription‑quantitative PCR. The association between serum lncRNA PTTG3P and clinical characteristics was further analyzed. Receiver operating characteristic (ROC) curve and area under curve (AUC) analyses were performed to estimate the diagnostic ability of serum lncRNA PTTG3P, PTTG1 and their combinations with other biomarkers for HCC. The results revealed that the expression levels of lncRNA PTTG3P and mRNA PTTG1 were markedly increased in the serum of patients with HCC and CHB compared with in the serum of HCs. Additionally, the postoperative levels of lncRNA PTTG3P and mRNA PTTG1 were significantly lower than the preoperative concentrations in 36 paired patients with HCC. Spearman's correlation coefficient analysis showed that serum lncRNA PTTG3P was correlated with aspartate transaminase (AST). ROC analysis showed that both lncRNA PTTG3P and mRNA PTTG1 had a significant predictive value for HCC. The AUC values of lncRNA PTTG3P and mRNA PTTG1 alone were 0.636 and 0.634, respectively. Furthermore, combining lncRNA PTTG3P, mRNA PTTG1, α‑fetoprotein (AFP), alanine aminotransferase (ALT), AST, γ‑glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) significantly increased the AUC value. The best performance was the combination of PTTG3P, PTTG1, AFP, ALT, AST, GGT and ALP with an AUC of 0.959, a sensitivity of 90.4% and a specificity of 98.0%. In conclusion, the combination of serum lncRNA PTTG3P, mRNA PTTG1 and AFP appeared to be a noninvasive biomarker with comparatively high specificity and sensitivity for the diagnosis of HCC.