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Simple Summary: In patients with high-risk prostate cancer (HRPC) after radical prostatectomy, biochemical recurrence increases the risk of distant metastasis. Therefore, complementary prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence after biochemical recurrence. This study was performed to identify prognostic factors for clinical recurrence in patients with HRPC who experience biochemical recurrence by conducting an analysis of the expression levels of snRNAs in formalin-fixed paraffin-embedded (FFPE) radical prostatectomy samples. The FFPE sample-derived snRNA RNU1-1/RNU1-2 could serve as an independent prognostic factor of clinical recurrence-free survival after biochemical recurrence of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between patients with clinical and non-clinical recurrence. Thus, snRNAs associated with prostate cancer may assist the early detection of clinical recurrence in patients with HRPC, allowing for more tailored and restorative treatments. In patients with high-risk prostate cancer (HRPC) after radical prostatectomy (RP), biochemical recurrence (BCR) increases the risk of distant metastasis. Accordingly, additional prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence (CR) after BCR. The objective of this study was to identify biomarkers in formalin-fixed paraffin-embedded (FFPE) RP samples that are prognostic for CR in patients with HRPC who experience BCR after RP (post-RP BCR). First, we performed a preliminary RNA sequencing analysis to comprehensively profile RNA expression in FFPE RP samples obtained from patients with HRPC who developed CR after post-RP BCR and found that many snRNAs were very abundant in preserved FFPE samples. Subsequently, we used quantitative polymerase chain reaction (qPCR) to compare the expression levels of highly abundant snRNAs in FFPE RP samples from patients with HRPC with and without CR after post-RP BCR (21 CR patients and 46 non-CR patients who had more than 5 years of follow-up after BCR). The qPCR analysis revealed that the expression levels of snRNA RNU1-1/1-2 and RNU4-1 were significantly higher in patients with CR than in patients without CR. These snRNAs were significantly correlated with clinical recurrence-free survival (RFS) in patients with HRPC who experienced post-RP BCR. Furthermore, snRNA RNU1-1/1-2 could serve as an independent prognostic factor for clinical RFS in post-RP BCR of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between CR and non-CR patients. Our findings provide new insights into the involvement of snRNAs in prostate cancer progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma is a highly malignant tumor with increasing prevalence worldwide. Extracellular vesicles exert their biological functions via the delivery of different biomolecules, including non-coding RNAs. In this review, the diverse roles of the non-coding RNA cargo of hepatocellular carcinoma-derived extracellular vesicles will be discussed. Their function in tumor progression, immune escape, and drug resistance, as well as their potentialvalue as biomarkers of disease, will be summarized. Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It is a major public health problem worldwide, and it is often diagnosed at advanced stages, when no effective treatment options are available. Extracellular vesicles (EVs) are nanosized double-layer lipid vesicles containing various biomolecule cargoes, such as lipids, proteins, and nucleic acids. EVs are released from nearly all types of cells and have been shown to play an important role in cell-to-cell communication. In recent years, many studies have investigated the role of EVs in cancer, including HCC. Emerging studies have shown that EVs play primary roles in the development and progression of cancer, modulating tumor growth and metastasis formation. Moreover, it has been observed that non-coding RNAs (ncRNAs) carried by tumor cell-derived EVs promote tumorigenesis, regulating the tumor microenvironment (TME) and playing critical roles in the progression, angiogenesis, metastasis, immune escape, and drug resistance of HCC. EV-related ncRNAs can provide information regarding disease status, thus encompassing a role as biomarkers. In this review, we discuss the main roles of ncRNAs present in HCC-derived EVs, including micro(mi) RNAs, long non-coding (lnc) RNAs, and circular (circ) RNAs, and their potential clinical value as biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: tRF-27 has been identified as upregulated in both naïve trastuzumab-resistant HER2-positive breast cancer cells and patient samples, positioning it as a potential biomarker. However, the underlying mechanisms of this upregulation remain unclear. This study proposes that the abnormal transcription of specific tRNA-Cys-GCA isodecoders in naïve trastuzumab-resistant cells might contribute to the accumulation of tRF-27. Additionally, the reduction in H3K27me3 modifications at these tRNA genes, attributed to imbalances in histone modification enzymes, appears to influence tRNA transcription alterations. Building upon these findings, our research demonstrates that the application of a demethylase inhibitor may offer a potential strategy to overcome trastuzumab resistance. tRNA-derived fragments (tRFs) play crucial roles in cancer progression. Among them, tRF-27 has been identified as a key factor in promoting naïve trastuzumab resistance in HER2-positive breast cancer. However, the origin of tRF-27 remains uncertain. In this study, we propose that the upregulated expression of specific cysteine tRNAs may lead to the increased accumulation of tRF-27 in trastuzumab-resistant JIMT1 cells. Mechanistically, the reduced inhibitory H3K27me3 modification at the promoter regions of tRF-27-related tRNA genes in JIMT1 cells, potentially resulting from decreased EZH2 and increased KDM6A activity, may be a critical factor stimulating the transcriptional activity of these tRNA genes. Our research offers fresh insights into the mechanisms underlying elevated tRF-27 levels in trastuzumab-resistant breast cancer cells and suggests potential strategies to mitigate trastuzumab resistance in clinical treatments. [ABSTRACT FROM AUTHOR]

Living organisms experience a range of stresses. To cope effectively with these stresses, eukaryotic cells have evolved a sophisticated mechanism involving the formation of stress granules (SGs), which play a crucial role in protecting various types of RNA species under stress, such as mRNAs and long non‐coding RNAs (lncRNAs). SGs are non‐membranous cytoplasmic ribonucleoprotein (RNP) granules, and the RNAs they contain are translationally stalled. Importantly, SGs have been thought to contribute to the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). SGs also contain multiple RNA‐binding proteins (RBPs), several of which have been implicated in AD progression. SGs are transient structures that dissipate after stress relief. However, the chronic stresses associated with aging lead to the persistent formation of SGs and subsequently to solid‐like pathological SGs, which could impair cellular RNA metabolism and also act as a nidus for the aberrant aggregation of AD‐associated proteins. In this paper, we provide a comprehensive summary of the physical basis of SG‐enriched RNAs and SG‐resident RBPs. We then review the characteristics of AD‐associated gene transcripts and their similarity to the SG‐enriched RNAs. Furthermore, we summarize and discuss the functional implications of SGs in neuronal RNA metabolism and the aberrant aggregation of AD‐associated proteins mediated by SG‐resident RBPs in the context of AD pathogenesis. Geriatr Gerontol Int 2024; 24: 7–14. [ABSTRACT FROM AUTHOR]

Background: The present research aims to investigate the clinical diagnostic value of LncRNA HOXA distal transcript antisense RNA (HOTTIP) in acute respiratory distress syndrome (ARDS) of sepsis and its predictive significance for mortality. Methods: One hundred eighteenth patients with sepsis and 96 healthy individuals were enrolled. RT-qPCR to examine HOTTIP levels. The incidence of ARDS and death was recorded. The diagnostic significance of HOTTIP in sepsis ARDS was examined using ROC and logistic regression analysis. The correlation between HOTTIP and disease severity was evaluated using Pearson's coefficients. Kaplan-Meier analysis and COX regression were employed to examine the predictive significance of mortality. Validation of HOTTIP target miRNA by dual-luciferase assay. Results: HOTTIP was persistently up-regulated in patients with ARDS sepsis than in patients without ARDS patients (P < 0.05). HOTTIP was a risk factor for the development of ARDS, which could be diagnosed in ARDS patients from non-ARDS patients (AUC = 0.847). Both the SOFA score (r = 0.6793) and the APACHE II score (r = 0.6384) were positively correlated with the HOTTIP levels. Furthermore, serum HOTTIP was an independent predictor of short-term mortality (HR = 4.813. 95%CI: 1.471–15.750, P = 0.009) and noticeably predicted the occurrence of short-term death (log rank = 0.020). miR-574-5p, a target miRNA for HOTTIP, was reduced in patients with sepsis ARDS and negatively correlated with HOTTIP. Conclusions: The presence of HOTTIP serves as a diagnostic biomarker for the occurrence of ARDS, exhibits correlation with disease severity, and provides predictive value of short-term mortality in sepsis patients. HOTTIP may be involved in ARDS progression by targeting miR-574-5p. [ABSTRACT FROM AUTHOR]

The objective of this study was to analyze the influence of long non-coding ribonucleic acid PGM5-AS1 on lung cancer cell ferroptosis through microrna-587. To this end, the research team has included the abnormal expression vectors of PGM5-AS1 and microrna-587 were transfected into human lung cancer cell line A549 to detect alterations in cell activity, apoptosis, cell cycle, oxidative stress, iron ion and ferroptosis-associated proteins. The results show silencing PGM5-AS1 or elevating microrna-587 promoted A549 proliferation and invasion, while inhibiting apoptosis and resisting ferroptosis. However, increasing PGM5-AS1 or silencing microrna-587 enhanced A549 apoptosis and induced ferroptosis (P < 0.05). And in the salvage experiment, the research team found that microrna-587 mimics inhibited PGM5-AS1-wild sequence fluorescence activity. The biological behavior of A549 after increasing (or silencing) PGM5-AS1 and microrna-587 was not different from that of cells transfected with microrna-587 negative control (P > 0.05). These results suggest that lowexpressed PGM5-AS1 can promote lung cancer cell viability, inhibit apoptosis and resist ferroptosis through targeted increase of microrna-587. [ABSTRACT FROM AUTHOR]

According to the prevailing view, the trap model, the activity of invading transposable elements (TEs) is greatly reduced when a TE copy jumps into a piRNA cluster, which triggers the emergence of piRNAs that silence the TE. One crucial component in the host defence are paramutations. Mediated by maternally deposited piRNAs, paramutations convert TE insertions into piRNA producing loci, thereby transforming selfish TEs into agents of the host defence. Despite this significant effect, the impact of paramutations on the dynamics of TE invasions remains unknown. To address this issue, we performed extensive forward simulations of TE invasions with piRNA clusters and paramutations. We found that paramutations significantly affect TE dynamics, by accelerating the silencing of TE invasions, reducing the number of insertions accumulating during the invasions and mitigating the fitness cost of TEs. We also demonstrate that piRNA production induced by paramutations, an epigenetically inherited trait, may be positively selected. Finally, we show that paramutations may account for three important open problems with the trap model. Firstly, paramutated TE insertions may compensate for the insufficient number of insertions in piRNA clusters observed in previous studies. Secondly, paramutations may explain the discrepancy between the observed and the expected abundance of different TE families in Drosophila melanogaster. Thirdly, piRNA clusters may be crucial to trigger the host defence, but paramutations render the clusters dispensable once the defence has been established. This could account for the lack of TE activation when three major piRNA clusters were deleted in a previous study. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a common malignant bone tumor. Cisplatin (DDP) achieves a high response rate in osteosarcoma. Here we aim to study the dysregulation of long non-coding RNA the growth arrest-specific transcript 5 (GAS5), and its roles in DDP-resistance of osteosarcoma. The expression of mRNA and microRNA in osteosarcoma tissues and osteosarcoma cell lines were detected by quantitative reverse-transcription polymerase chain reaction, and protein expression levels were measured by western blotting assay. Cell Counting Kit-8 and 5-Ethynyl-2′-deoxyuridine were used to measure cell proliferation. Flow cytometer assay was used to evaluate cell apoptosis. The interactions between miR-26b-5p and GAS5 or tumor protein p53-induced nuclear protein 1 (TP53INP1) were verified by dual luciferase reporter along with biotin RNA pull-down assays. GAS5 was identified to be significantly lowly expressed in osteosarcoma samples especially in cisplatin-resistant (DDP-resistant) tissues. GAS5 was also downregulated in DDP-resistant cells. Over-expressed GAS5 prominently increased the sensitivity of osteosarcoma cells to DDP in vitro. Furthermore, over-expression of GAS5 suppressed cell proliferation and facilitated apoptosis of DDP-resistant cells. Mechanistically, GAS5 sponged miR-26b-5p, over-expression of which reversed the effects of GAS5 on cell proliferation and apoptosis of DDP-resistant cells. In addition, miR-26b-5p targeted TP53INP1. TP53INP1 abrogated the functions of miR-26b-5p on cell proliferation and apoptosis in DDP-resistant cells. Taken together, GAS5 enhanced the sensitivity of osteosarcoma cells to DDP via GAS5/miR-26b-5p/TP53INP1 axis. Therefore, GAS5 may be a potential indicator for the management of osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: We have previously shown that remote ischemic preconditioning (RIP), which utilizes in part the extracellular RNA (eRNA)/RNase1 pathway, can induce ischemic tolerance in humans. Because RIP has thus far been tested only with four cycles of extremity ischemia/reperfusion, we investigated the influence of six cycles of ischemia on the eRNA/RNase1 pathway in cardiac patients. Methods: Six cycles of RIP were carried out in 14 patients undergoing cardiac surgery. Blood samples were taken at 13 timepoints during surgery and at three timepoints after surgery for determining serum levels of RNase1, eRNA, and TNF-α. Trans-cardiac gradients between the myocardial blood inflow and outflow were calculated. Results: Between the fourth and the sixth RIP cycles, a noticeable increase in the levels of eRNA (fourth: 151.6 (SD: 44.2) ng/ml vs sixth: 181.8 (SD: 87.5) ng/ml, p =.071), and a significant increase in RNase1 (fourth: 151.1 (SD: 42.6) U/ml vs sixth: 175.3 (SD: 41.2) U/ml, p =.001), were noted. The trans-cardiac gradients of RNase1 and eRNA before and after ischemia were not significantly different (p =.158 and p =.221; p =.397 and p =.683, respectively). Likewise, the trans-cardiac gradient of TNF-α was similar before and after ischemia. During the first 48 h after the surgery, RNase1 activity rose significantly and exceeded baseline values (135.7 (SD: 40.6) U/ml before and 279.2 (SD: 85.6) U/ml after surgery, p =.001) as did eRNA levels (148,6 (SD: 35.4) ng/ml before and 396.5 (SD: 154.5) ng/ml after surgery, p =.005), whereas TNF-α levels decreased significantly (91.7 (SD: 47.7) pg/ml before and 35.7 (SD: 36.9) pg/ml after surgery, p =.001). Conclusion: Six RIP cycles increased the RNase1 levels significantly above those observed with four cycles. More clinical data are required to show whether this translates into a benefit for patients. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss (RPL) or recurrent miscarriage is the failure of pregnancy before 20-24 weeks that influences around 2-5% of couples. Several genetic, immunological, environmental and physical factors may influence RPL. Although various traditional methods have been used to treat post-implantation failures, identifying the mechanisms underlying RPL may improve an effective treatment. Recent evidence suggested that gene expression alterations presented essential roles in the occurrence of RPL. It has been found that long non-coding RNAs (lncRNAs) play functional roles in pregnancy pathologies, such as recurrent miscarriage. lncRNAs can function as dynamic scaffolds, modulate chromatin function, guide and bind to microRNAs (miRNAs) or transcription factors. lncRNAs, by targeting various miRNAs and mRNAs, play essential roles in the progression or suppression of RPL. Therefore, targeting lncRNAs and their downstream targets might be a suitable strategy for diagnosis and treatment of RPL. In this review, we summarized emerging roles of several lncRNAs in stimulation or suppression of RPL. [ABSTRACT FROM AUTHOR]

Simple Summary: Myelodysplastic neoplasms (MDS) are a group of hematologic malignancies with an increased risk of transformation to acute myeloid leukemia. Non-coding RNAs are RNA molecules of variable size that do not translate into proteins but regulate gene expression during multiple cellular processes. These RNAs have been found deregulated in several cancers, including MDS. In this review, we aim to summarize research findings on the biological role of different non-coding RNAs in MDS development and progression, with emphasis on molecules that have exhibited prognostic or predictive value and could, hence, guide decision-making in clinical practice. Myelodysplastic syndromes or neoplasms (MDS) are a heterogeneous group of myeloid clonal disorders characterized by peripheral blood cytopenias, blood and marrow cell dysplasia, and increased risk of evolution to acute myeloid leukemia (AML). Non-coding RNAs, especially microRNAs and long non-coding RNAs, serve as regulators of normal and malignant hematopoiesis and have been implicated in carcinogenesis. This review presents a comprehensive summary of the biology and role of non-coding RNAs, including the less studied circRNA, siRNA, piRNA, and snoRNA as potential prognostic and/or predictive biomarkers or therapeutic targets in MDS. [ABSTRACT FROM AUTHOR]

Esophageal carcinoma (ESCA) is one of the prevalent malignancies worldwide. Cisplatin (CDDP) is a conventional chemotherapy drug. However, the acquired cisplatin resistance limits its extensively clinical applications. In this study, the roles and underlying mechanisms of lncRNA PVT1 in cisplatin-resistant ESCA are investigated. PVT1 was significantly upregulated in ESCA patient specimens and cell lines. Higher PVT1 level was associated with a poor survival rate of ESCA patients. Silencing PVT1 effectively increased cisplatin sensitivity of ESCA cells. We established cisplatin-resistant ESCA cell line (EC109 CDDP Res) and detected that PVT1 and glutamine metabolism were remarkedly elevated in CDDP-resistant esophageal cancer cells. Bioinformatical analysis and luciferase assay illustrated that PVT1 sponged miR-181a-5p to form a ceRNA network, resulting in the downregulation of miR-181a-5p expression in ESCA cells. Glutaminase (GLS), which is a key enzyme in the glutamine metabolism, was identified and validated as a direct target of miR-181-5p in ESCA cells. Inhibiting glutamine metabolism effectively re-sensitized CDDP-resistant cells. Rescue experiments demonstrated that restoration of miR-181a-5p in PVT1-overexpressing CDDP-resistant ESCA cells successfully overcame the PVT1-promoted cisplatin resistance through targeting GLS. Summarily, our study revealed molecular mechanisms of the lncRNA PVT1-promoted cisplatin resistance in ESCA by modulating the miR-181a-5p-GLS axis. [ABSTRACT FROM AUTHOR]

Simple Summary: The human genome produces various types of RNA molecules. A significant portion of these are long non-coding RNAs (lncRNAs) exceeding 200 nts without an obvious open reading frame. There are more than 200,000 lncRNAs, but we have limited understanding of their functions. LncRNAs can influence gene activity by interacting with proteins or nucleic acids. Some lncRNAs regulate genes involved in cancer, either promoting or suppressing tumor growth. One lncRNA of interest is ANRIL (Antisense Noncoding RNA in the INK4 Locus), which can affect gene expression through different ways. However, ANRIL's exact role in cancer is complex and varies in different situations, making it a challenging area to study. This review strives to offer a thorough comprehension of ANRIL's role in regulating genes and its impact on the development of cancer. ANRIL (Antisense Noncoding RNA in the INK4 Locus), a long non-coding RNA encoded in the human chromosome 9p21 region, is a critical factor for regulating gene expression by interacting with multiple proteins and miRNAs. It has been found to play important roles in various cellular processes, including cell cycle control and proliferation. Dysregulation of ANRIL has been associated with several diseases like cancers and cardiovascular diseases, for instance. Understanding the oncogenic role of ANRIL and its potential as a diagnostic and prognostic biomarker in cancer is crucial. This review provides insights into the regulatory mechanisms and oncogenic significance of the 9p21 locus and ANRIL in cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Long non-coding RNAs (lncRNAs) are a large class of RNA molecules known to regulate the expression of genes. Although expressed in a highly tissue-specific manner, they appear to modulate virtually all pathways in the cell, either in normal or disease states. LncRNAs are often aberrantly expressed in cancers and can act as oncogenes or tumor suppressors. Here, we describe various mechanisms by which lncRNAs influence gene expression as they bind other RNAs, genomic DNA, or proteins. Particularly, we discuss their relationship with transcription factors as they act on pathways relevant to cancer. While much remains to be discovered about how they regulate genes, lncRNAs hold great therapeutic potential, especially in their transcription factor interactions. As a group of diseases characterized by uncontrollable cell growth, cancer is highly multifaceted in how it overrides checkpoints controlling proliferation. Amongst the regulators of these checkpoints, long non-coding RNAs (lncRNAs) can have key roles in why natural biological processes go haywire. LncRNAs represent a large class of regulatory transcripts that can localize anywhere in cells. They were found to affect gene expression on many levels from transcription to mRNA translation and even protein stability. LncRNA participation in such control mechanisms can depend on cell context, with given transcripts sometimes acting as oncogenes or tumor suppressors. Importantly, the tissue-specificity and low expression levels of lncRNAs make them attractive therapeutic targets or biomarkers. Here, we review the various cellular processes affected by lncRNAs and outline molecular strategies they use to control gene expression, particularly in cancer and in relation to transcription factors. [ABSTRACT FROM AUTHOR]

Simple Summary: Long non-coding RNAs (LncRNAs) are non-protein coding molecules longer than 200 nucleotides. They play essential roles in normal cell function and development, and can contribute to diseases such as cancer when dysregulated. Although lncRNAs have oncogenic or tumor-suppressive properties in lung cancer and can serve as stable biomarkers, this is still an understudied field. Here, we discuss recent evidence for lncRNAs role in lung cancer development, therapy resistance, biomarker potential, and therapeutic strategies. We conclude that understanding the interplay between non-coding and coding molecules in lung cancer should be explored further and may open up new avenues for treatment. Long non-coding RNAs (LncRNAs) are mRNA-like molecules that do not encode for proteins and that are longer than 200 nucleotides. LncRNAs play important biological roles in normal cell physiology and organism development. Therefore, deregulation of their activities is involved in disease processes such as cancer. Lung cancer is the leading cause of cancer-related deaths due to late stage at diagnosis, distant metastasis, and high rates of therapeutic failure. LncRNAs are emerging as important molecules in lung cancer for their oncogenic or tumor-suppressive functions. LncRNAs are highly stable in circulation, presenting an opportunity for use as non-invasive and early-stage cancer diagnostic tools. Here, we summarize the latest works providing in vivo evidence available for lncRNAs role in cancer development, therapy-induced resistance, and their potential as biomarkers for diagnosis and prognosis, with a focus on lung cancer. Additionally, we discuss current therapeutic approaches to target lncRNAs. The evidence discussed here strongly suggests that investigation of lncRNAs in lung cancer in addition to protein-coding genes will provide a holistic view of molecular mechanisms of cancer initiation, development, and progression, and could open up a new avenue for cancer treatment. [ABSTRACT FROM AUTHOR]

Objective: The role and molecular mechanism of long-chain noncoding RNAs (lncRNAs) in lung cancer remain to be elucidated. The aim of this study was to investigate the association between a long coding RNA hypoxia-inducible factor-2α (HIF-2α) promoter upstream transcript (HIF2PUT) and clinical characteristics of non-small cell lung cancer (NSCLC) and its regulatory role in NSCLC. Materials and Methods: The correlation between HIF2PUT expression and pathological features of NSCLC was analyzed in NSCLC patient samples. Real-time polymerase chain reaction and Western blot were used to detect genes' mRNA and protein expression, respectively. Cell proliferation assay, invasion, and transwell assay were performed to determine the effects of HIF2PUT on NSCLC cells. Results: lncRNA HIF2PUT was downregulated in NSCLC tissues and cell lines. The authors found that HIF2PUT was mainly expressed in cytoplasm and overexpression of HIF2PUT attenuates cell proliferation and invasion in NSCLC cells. Moreover, low expression of HIF2PUT was significantly related to TNM stage (p = 0.045) and histological type (p = 0.025). Furthermore, HIF2PUT was found to play a role in cell proliferation and invasion in NSCLC through regulating HIF-2a. Conclusion: Based on this study, the inhibitory role of HIF2PUT on NSCLC proliferation, invasion could be blocked by HIF-2a silencing. In summary, this study suggests that HIF2PUT and HIF-2a may play an important role in the regulation of NSCLC progression, which provides new insights for clinical treatment. [ABSTRACT FROM AUTHOR]

Objective: Cuproptosis‐related genes are closely related to lung adenocarcinoma (LUAD), which can be analyzed via the analysis of long noncoding RNA (lncRNA). To date, the clinical significance and function of cuproptosis‐related lncRNAs are still not well elucidated. Further analysis of cuproptosis‐related prognostic lncRNAs is of great significance for the treatment, diagnosis, and prognosis of LUAD. Methods: In this study, a multiple machine learning (ML)‐based computational approach was proposed for the identification of the cuproptosis‐related lncRNAs signature (CRlncSig) via comprehensive analysis of cuproptosis, lncRNAs, and clinical characteristics. The proposed approach integrated multiple ML algorithms (least absolute shrinkage and selection operator regression analysis, univariate and multivariate Cox regression) to effectively identify the CRlncSig. Results: Based on the proposed approach, the CRlncSig was identified from the 3450 cuproptosis‐related lncRNAs, which consist of 13 lncRNAs (CDKN2A‐DT, FAM66C, FAM83A‐AS1, AL359232.1, FRMD6‐AS1, AC027237.4, AC023090.1, AL157888.1, AL627443.3, AC026355.2, AC008957.1, AP000346.1, and GLIS2‐AS1). Conclusions: The CRlncSig could well predict the prognosis of different LUAD patients, which is different from other clinical features. Moreover, the CRlncSig was proved to be an effective indicator of patient survival via functional characterization analysis, which is relevant to cancer progression and immune infiltration. Furthermore, the results of RT‐PCR assay indicated that the expression level of FAM83A‐AS1 and AC026355.2 in A549 and H1975 cells (LUAD) was significantly higher than that in BEAS‐2B cells (normal lung epithelial). [ABSTRACT FROM AUTHOR]

Objective: This study aimed to profile differentially expressed (DE) exosomal RNAs in healthy subjects and periodontitis patients and compare their levels before and after treatment. Materials and methods: Plasma samples from healthy subjects and patients with periodontitis (pre‐/post‐periodontal treatment) were collected for this case–control study. After isolation of exosomes from the plasma, the RNA was extracted and small RNA sequencing was performed (3 healthy samples, 4 pre‐treatment samples, and 5 post‐treatment samples). Two‐way analyses were conducted according to the treatment status in the periodontitis group, unpaired analysis (grouping as pre‐/post‐treatment) and paired analysis (matching pre‐ and post‐treatment in the same subject). The DE exosomal RNAs were screened by sequencing and visualized using the R software. Gene Ontology analysis was performed, and target genes were identified. Results: In both paired and unpaired analyses, two DE microRNAs (DEmiRs; miR‐1304‐3p and miR‐200c‐3p) and two DE small nucleolar RNAs (DEsnoRs; SNORD57 and SNODB1771) were common, and they were found to be downregulated during periodontitis and recovered to healthy levels after treatment. The top three target genes (NR3C1, GPR158, and CNN3) commonly regulated by DEmiRs were identified. Conclusions: Plasma‐derived exosomal miRs (miR‐1304‐3p and miR‐200c‐3p) and snoRs (SNORD57 and SNODB1771) could be valuable biomarkers for periodontitis. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer cells generally release special vesicles (exosomes) showing tumor-promoting effects. Some natural products blocking exosome processing (assembly and secretion) can inhibit cancer progression. Long noncoding RNAs (lncRNAs), enclosed in exosomes, can bind and modulate several microRNAs (miRNAs), and, in turn, miRNAs can regulate their targets, such as exosome processing genes. However, there is a gap in the correlation between exosomal lncRNAs and exosomal processing of natural product treatments. After collecting and organizing literature reports, we introduce bioinformatics for retrieving miRNA targets of lncRNAs and exosomal processing gene targets of miRNAs to fill this gap. Consequently, the function of exosomal lncRNAs of cancer cells in regulating miRNA targets that potentially modulate exosomal processing genes is summarized, particularly for the anticancer effects of natural products. Cancerous exosomes contain diverse biomolecules that regulate cancer progression. Modulating exosome biogenesis with clinical drugs has become an effective strategy for cancer therapy. Suppressing exosomal processing (assembly and secretion) may block exosomal function to reduce the proliferation of cancer cells. However, the information on natural products that modulate cancer exosomes lacks systemic organization, particularly for exosomal long noncoding RNAs (lncRNAs). There is a gap in the connection between exosomal lncRNAs and exosomal processing. This review introduces the database (LncTarD) to explore the potential of exosomal lncRNAs and their sponging miRNAs. The names of sponging miRNAs were transferred to the database (miRDB) for the target prediction of exosomal processing genes. Moreover, the impacts of lncRNAs, sponging miRNAs, and exosomal processing on the tumor microenvironment (TME) and natural-product-modulating anticancer effects were then retrieved and organized. This review sheds light on the functions of exosomal lncRNAs, sponging miRNAs, and exosomal processing in anticancer processes. It also provides future directions for the application of natural products when regulating cancerous exosomal lncRNAs. [ABSTRACT FROM AUTHOR]

Objective: Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been reported to exert regulatory effects on biological processes. This study intended to assess the role of the lncRNA HOXA transcript at the distal tip (HOTTIP)/miR-30b-3p/phosphoglycerate kinase 1 (PGK1) axis in ankylosing spondylitis (AS). Methods: Levels of HOTTIP, miR-30b-3p and PGK1 in AS synovial tissues and cultured AS fibroblast-like synoviocytes (ASFLSs) were assessed. The ASFLSs were identified and, respectively, treated with altered expression of HOTTIP and miR-30b-3p, and then, the proliferation and differentiation of the ASFLSs were assessed. The AS mouse models were established by injection of proteoglycan and Freund's complete adjuvant and then were treated with altered expression of HOTTIP and miR-30b-3p, and the pathological changes and apoptosis of synoviocytes in mice' synovial tissues were measured. The relationship of HOTTIP, miR-30b-3p and PGK1 was verified. Results: HOTTIP and PGK1 were elevated, while miR-30b-3p was reduced in AS synovial tissues and ASFLSs. Elevated miR-30b-3p or inhibited HOTTIP restrained proliferation and differentiation of ASFLSs and also improved the pathological changes and promoted apoptosis of synoviocytes in mice's synovial tissues. PGK1 was a target of miR-30b-3p, and miR-30b-3p could directly bind to HOTTIP. Silencing miR-30b-3p or overexpressing PGK1 reversed the improvement of AS by knocking down HOTTIP or up-regulating miR-30b-3p. Conclusion: Our study suggests that reduced HOTTIP ameliorates AS progression by suppressing the proliferation and differentiation of ASFLSs through the interaction of miR-30b-3p and PGK1. [ABSTRACT FROM AUTHOR]

The present study was developed to explore whether microRNA (miR)-760 targets heparin-binding EGF-like growth factor (HBEGF) to control cartilage extracellular matrix degradation in osteoarthritis. Both miR-760 and HBEGF expression levels were analysed in human degenerative cartilage tissues and in interleukin (IL)-1β/tumour necrosis factor (TNF)-α-treated chondrocytes in vitro. A series of knockdown and overexpression assays were then used to gauge the functional importance of miR-760 and HBEGF in OA, with qPCR and western immunoblotting analyses. Bioinformatics assays were used to identify putative miR-760 target genes, with these predictions then being validated through RNA pulldown and luciferase reporter assays. A murine anterior cruciate ligament transection model of OA was then established to prove the in vivo relevance of these findings. These experiments revealed that human degenerative cartilage tissues exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF levels. IL-1β/TNF-α-treated chondrocytes also exhibited significant increases in miR-760 expression with a concomitant drop in HBEGF expression. When chondrocytes were transfected with either miR-760 inhibitor or HBEGF overexpression constructs, this was sufficient to interfere with degradation of the extracellular matrix (ECM). Moreover, miR-760 was confirmed to control chondrocyte matrix homeostasis by targeting HBEGF, and the overexpression of HBEGF partially reversed the effects of miR-760 mimic treatment on the degradation of the cartilage ECM. When OA model mice were administered an intra-articular knee injection of an adenoviral vector encoding a miR-760 mimic construct, cartilage ECM degradation was aggravated. Conversely, the overexpression of HBEGF in OA model mice partially reversed the effects of miR-760 overexpression, restoring appropriate ECM homeostasis. In summary, these data indicated that the miR-760/HBEGF axis plays a central role in orchestrating the pathogenesis of OA, making it a candidate target for therapeutic efforts in OA. [ABSTRACT FROM AUTHOR]

Objective: LncRNA IUR has been recently identified as a key regulator of Bcr-Abl-induced tumorigenesis, while its role in gastric carcinoma (GC) is unknown. This study investigated the involvement of IUR in GC. Materials and Methods: Gene expression levels were measured by performing quantitative polymerase chain reaction. Interactions between IUR and ROCK1 were analyzed by transfection experiments. Cell invasion and migration were analyzed by Transwell assay. Results: In this study, the authors showed that IUR was downregulated in GC. A follow-up study showed that low IUR expression levels predicted poor survival. In GC tissues, ROCK1 was upregulated in GC tissues and inversely correlated with IUR. In GC cells, IUR overexpression mediated the downregulation of ROCK1. ROCK1 overexpression resulted in increased GC cell invasion and migration, while IUR overexpression played an opposite role. Conclusion: IUR is downregulated in GC and inhibits GC cell invasion and migration by downregulating ROCK1. [ABSTRACT FROM AUTHOR]

Aim: Long non‐coding RNAs were widely reported to regulate laryngeal squamous cell carcinoma (LSCC), a prevalent tumor in the head and neck. We aimed to investigate the role of solute carrier organic anion transporter family member 4A1 antisense RNA 1 (SLCO4A1‐AS1) in LSCC. Materials & methods: CCK‐8 and colony formation assays were conducted to examine the viability and proliferation of LSCC cells. The apoptosis of LSCC cells was evaluated using flow cytometry and TUNEL assays. The distribution of SLCO4A1‐AS1 in LSCC cells was detected by subcellular fractionation assay. The interaction between molecules was confirmed using luciferase reporter assay. Results: SLCO4A1‐AS1 was overexpressed in LSCC tissues and cells. Furthermore, silenced SLCO4A1‐AS1 repressed the proliferation and facilitated apoptosis of LSCC cells. Mechanistical investigation revealed that SLCO4A1‐AS1 was a competing endogenous RNA (ceRNA) to upregulate SETD7 by binding with miR‐7855‐p. Additionally, SLCO4A1‐AS1 positively regulated the Wnt/β‐catenin signaling pathway by upregulating SETD7. Rescue experiments demonstrated that SLCO4A1‐AS1 promoted LSCC proliferation and inhibited LSCC apoptosis by upregulation of SETD7 and activation of the Wnt/β‐catenin pathway. Conclusion: SLCO4A1‐AS1 promotes proliferation and inhibits apoptosis of LSCC cells by upregulation of SETD7 in a miR‐7855‐5p dependent way to activate the Wnt/β‐catenin pathway. [ABSTRACT FROM AUTHOR]

Glioma is the most common tumor in the central nervous system. High-grade gliomas confer a poor prognosis, being a serious health and economic burden. Current literature suggests the important role of long noncoding RNA (lncRNA) in mammals, especially in tumorigenesis of various tumors. The functions of lncRNA POU3F3 adjacent noncoding transcript 1 (PANTR1) have been investigated in hepatocellular carcinoma but remain yet unclear in gliomas. We evaluated the role of PANTR1 in glioma cells using published data from The Cancer Genome Atlas (TCGA), then validated it by ex vivo experiments. To investigate the potential cellular mechanism of different levels of PANTR1 expression in glioma cells, we used siRNA-mediated knockdown in low-grade (grade II) cell lines and GBM (grade IV) cell lines (SW1088 and SHG44, respectively). On the molecular level, low expression of PANTR1 caused significantly reduced glioma cell viability and enhanced cell death. Moreover, we identified the importance of PANTR1 expression for cell migration in both cell lines, a critical foundation for invasiveness in recurrent gliomas. In conclusion, this study provides the first evidence that PANTR1 has a relevant role in human glioma by influencing cell viability and cell death. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been reported to be involved in the development and progression of various human malignancies. However, the role of lncRNA CASC2 in hepatocellular carcinoma (HCC) remains mostly unknown. The aim of this study was to investigate the potential roles and underlying mechanisms of CASC2 in HCC progression. We found that CASC2 expressions were downregulated in HCC tissue samples and cell lines. The clinical assays revealed that lower levels of CASC2 were associated with the TNM stage, lymph node metastasis, and a poorer prognosis specific to HCC patients. Overexpression of CASC2 inhibited the proliferating, migratory, and invasion capacity of HCC cells. Bioinformatics analysis and the luciferase reporter assay revealed that CASC2 worked as a molecular sponge for miR-155. And CASC2 could upregulate SOCS1 expression by inhibiting miR-155 expression in HCC cells. Furthermore, SOCS1 inhibition partially inverses the suppression effect of cell proliferation, migration, and invasion regulated by CASC2 in Huh7 and HepG2 cells. Taken together, our findings identified CASC2 as a tumor suppressor to inhibit HCC development by regulating the miR-155/SOCS1 axis, and CASC2 might be a potential therapeutic target of HCC for future clinical treatment. [ABSTRACT FROM AUTHOR]

Long noncoding (lnc) RNAs regulate cancer progression. However, the importance of lncRNAs and how they are regulated in colorectal cancer (CRC) are unclear. We aim to evaluate the function of lncRNA ADAMTS9-AS2 in CRC and its fundamental mechanism. Levels of ADAMTS9-AS2, miR-27a-3p, and B-cell translocation gene 2 (BTG2) were measured by qPCR. Cell viability was analyzed by CCK-8 and colony formation. Migration and invasion were tested by transwell assay. The interactions among ADAMTS9-AS2, miR-27a-3p, BTG2, and YTHDF2 were analyzed by luciferase test, immunoblotting, RNA pull-down, or RNA immunoprecipitation (RIP). An animal model was adopted to assess ADAMTS9-AS2's function. Overexpressing ADAMTS9-AS2 inhibited cell migration, invasion, colony formation capacity, and proliferation in vitro. The direct targeting of miR-27a-3p by ADAMTS9-AS2 abrogated the latter's effect in CRC cells. BTG2 was identified a target of miR-27a-3p, and silencing BTG2 weakened miR-27a-3p's effect. Knocking down ADAMTS9-AS2 abolished sh-YTHDF2's inhibitory effect on cell proliferation and invasion. Finally, overexpressing ADAMTS9-AS2 restrained xenograft growth. M6A reader YTHDF2-mediated degradation of ADAMTS9-AS2 promotes colon carcinogenesis via miR-27a-3p/BTG2 axis. [ABSTRACT FROM AUTHOR]

Simple Summary: Exosomes are nanosized vesicles secreted by living cells and exist in biological fluids. Exosomes contain various bioactive molecules, including proteins, nucleic acids, and lipids, which can reflect the pathophysiological state of donor cells. In recent years, long non-coding RNAs (lncRNAs) in exosomes have attracted wide attention in cancer research. Exosomal lncRNAs play important roles in gastrointestinal cancer progression. Blood samples-derived exosomal lncRNAs also exhibit great potential to serve as important indicators of liquid biopsy, thus providing a novel diagnosis strategy for gastrointestinal cancer. In addition, exosomes-mediated several lncRNAs delivery can exert anti-tumor effects. The aim of this review article is to summarize the recent work conducted in this field and evaluate the opportunities and challenges in utilizing exosomal lncRNAs for the diagnostic and therapeutic purposes of gastrointestinal cancer in the clinical setting. Due to the lack of specific and effective biomarkers and therapeutic targets, the early diagnosis and treatment of gastrointestinal cancer remain unsatisfactory. As a type of nanosized vesicles derived from living cells, exosomes mediate cell-to-cell communication by transporting bioactive molecules, thus participating in the regulation of many pathophysiological processes. Recent evidence has revealed that several long non-coding RNAs (lncRNAs) are enriched in exosomes. Exosomes-mediated lncRNAs delivery is critically involved in various aspects of gastrointestinal cancer progression, such as tumor proliferation, metastasis, angiogenesis, stemness, immune microenvironment, and drug resistance. Exosomal lncRNAs represent promising candidates to act as the diagnosis biomarkers and anti-tumor targets. This review introduces the major characteristics of exosomes and lncRNAs and describes the biological functions of exosomal lncRNAs in gastrointestinal cancer development. The preclinical studies on using exosomal lncRNAs to monitor and treat gastrointestinal cancer are also discussed, and the opportunities and challenges for translating them into clinical practice are evaluated. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with lung cancer have high rates of brain metastasis (BM). Despite available therapies, patient prognosis is poor. Studies have shown genetic alterations associated with the metastatic spread of lung cancer cells. However, the precise mechanisms governing BM are still unclear. In this review, we comprehensively describe the major steps of metastatic spread of lung cancer to the brain, addressing the influence of the tumor microenvironment and the molecular determinants of progression. Furthermore, we highlight the advances in the molecular diagnostics of BM by liquid biopsies and discuss novel treatment strategies. Lung cancer is one of the most frequent tumors that metastasize to the brain. Brain metastasis (BM) is common in advanced cases, being the major cause of patient morbidity and mortality. BMs are thought to arise via the seeding of circulating tumor cells into the brain microvasculature. In brain tissue, the interaction with immune cells promotes a microenvironment favorable to the growth of cancer cells. Despite multimodal treatments and advances in systemic therapies, lung cancer patients still have poor prognoses. Therefore, there is an urgent need to identify the molecular drivers of BM and clinically applicable biomarkers in order to improve disease outcomes and patient survival. The goal of this review is to summarize the current state of knowledge on the mechanisms of the metastatic spread of lung cancer to the brain and how the metastatic spread is influenced by the brain microenvironment, and to elucidate the molecular determinants of brain metastasis regarding the role of genomic and transcriptomic changes, including coding and non-coding RNAs. We also present an overview of the current therapeutics and novel treatment strategies for patients diagnosed with BM from NSCLC. [ABSTRACT FROM AUTHOR]

Background: Guided bone self-generation with periosteum-preserved has successfully regenerated mandibular, temporomandibular and interphalangeal joint. The aim of this study was to investigate the dynamic changes of gene expression of periosteum which was involved in the guided bone self-generation. Methods: Rib defects of critical size were created in mature swine with periosteum-preserved. The periosteum was sutured into a sealed sheath that closed the bone defect. The periosteum of trauma and control sites were harvested at postoperative 9 time points, and total RNA was extracted. Microarray analysis was conducted to identify the differences in the transcriptome of different time points between two groups. Results: The differentially expressed genes (DEGs) between control and trauma group were different at postoperative different time points. The dynamic changes of the number of DEGs fluctuated a lot. There were 3 volatility peaks, and we chose 3 time points of DEG number peak (1 week, 5 weeks and 6 months) to study the functions of DEGs. Oxidoreductase activity, oxidation–reduction process and mitochondrion are the most enriched terms of Go analysis. The major signaling pathways of DEGs enrichment include oxidative phosphorylation, PI3K-Akt signaling pathway, osteoclast differentiation pathway and Wnt signaling. Conclusions: The oxidoreductase reaction was activated during this bone regeneration process. The oxidative phosphorylation, PI3K-Akt signaling pathway, osteoclast differentiation pathway and Wnt signaling may play important roles in the guided bone self-generation with periosteum-preserved. This study can provide a reference for how to improve the application of this concept of bone regeneration. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatocellular carcinoma (HCC) remains a major health concern. Immunotherapy combined with targeted therapy brings hope to patients with HCC, but its primary beneficiaries have not been identified. Recent studies have found that copper induces cell death, which is named cuproptosis. As we know, cell death is closely related to tumor therapy, in which some non-coding RNAs involved. Therefore, we focused on whether some long non-coding RNAs (LncRNAs) are related to cuproptosis, and the cuproptosis-related LncRNAs (crLncRNAs) can classify tumor treatment-sensitive populations. In the study, we explore a model of crLncRNAs with excellent specificity and sensitivity that is capable of predicting the prognosis of HCC patients and classifying tumor immunotherapy-sensitive populations, thereby providing new insights for the development of appropriate clinical strategies. Immunotherapy has shown strong anti-tumor activity in a subset of patients. However, many patients do not benefit from the treatment, and there is no effective method to identify sensitive immunotherapy patients. Cuproptosis as a non-apoptotic programmed cell death caused by excess copper, whether it is related to tumor immunity has attracted our attention. In the study, we constructed the prognostic model of 9 cuproptosis-related LncRNAs (crLncRNAs) and assessed its predictive capability, preliminarily explored the potential mechanism causing treatment sensitivity difference between the high-/low-risk group. Our results revealed that the risk score was more effective than traditional clinical features in predicting the survival of HCC patients (AUC = 0.828). The low-risk group had more infiltration of immune cells (B cells, CD8+ T cells, CD4+ T cells), mainly with anti-tumor immune function (p < 0.05). It showed higher sensitivity to immune checkpoint inhibitors (ICIs) treatment (p < 0.001) which may exert the effect through the AL365361.1/hsa-miR-17-5p/NLRP3 axis. In addition, NLRP3 mutation-sensitive drugs (VNLG/124, sunitinib, linifanib) may have better clinical benefits in the high-risk group. All in all, the crLncRNAs model has excellent specificity and sensitivity, which can be used for classifying the therapy-sensitive population and predicting the prognosis of HCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Heavy-ion radiotherapy (HIRT) is associated with higher tumor cure rates compared with conventional radiotherapy (CRT). However, considering the high cost of HIRT, most tumor patients are still treated with CRT. The aim of this study was to elucidate the tumor inhibitory mechanism of HIRT by exploring gene expression signatures after heavy-ion exposure. We confirmed that the carbon ion-responsive long non-coding RNA endogenous bornavirus-like nucleoprotein 3, pseudogene (EBLN3P), is significantly decreased in carbon-ion irradiated non-small cell lung cancer (NSCLC) cells. The combination therapy of LNC EBLN3P-inhibition and X-ray irradiation can delay the progression of NSCLC both in vitro and in vivo, indicating the potential role of LNC EBLN3P as a target of radiosensitization in CRT. In recent decades, the rapid development of radiotherapy has dramatically increased the cure rate of malignant tumors. Heavy-ion radiotherapy, which is characterized by the "Bragg Peak" because of its excellent physical properties, induces extensive unrepairable DNA damage in tumor tissues, while normal tissues in the path of ion beams suffer less damage. However, there are few prognostic molecular biomarkers that can be used to assess the efficacy of heavy ion radiotherapy. In this study, we focus on non-small cell lung cancer (NSCLC) radiotherapy and use RNA sequencing and bioinformatic analysis to investigate the gene expression profiles of A549 cells exposed to X-ray or carbon ion irradiation to screen the key genes involved in the stronger tumor-killing effect induced by carbon ions. The potential ceRNA network was predicted and verified by polymerase chain amplification, western blotting analysis, colony formation assay, and apoptosis assay. The results of the experiments indicated that lncRNA EBLN3P plays a critical role in inhibiting carbon ion-induced cell proliferation and inducing apoptosis of NSCLC cells. These functions were achieved by the EBLN3P/miR-144-3p/TNPO1 (transportin-1) ceRNA network. In summary, the lncRNA EBLN3P functions as a ceRNA to mediate lung cancer inhibition induced by carbon ion irradiation by sponging miR-144-3p to regulate TNPO1 expression, indicating that EBLN3P may be a promising target for increasing the treatment efficacy of conventional radiotherapy for NSCLC. [ABSTRACT FROM AUTHOR]

Arsenic (As) exposure has been a global public health concern for hundreds of millions worldwide. LncRNA APTR (Alu-mediated p21 transcriptional regulator) plays an essential role in tumor growth and development. However, its function in arsenic-induced toxicological responses is still unknown. In this study, we found that the expressions of all transcripts and the transcript NR 134251.1 of APTR were increased in a dose-dependent manner in 16HBE cells treated with sodium arsenite (NaAsO2). Silencing the transcript NR 134251.1 of APTR inhibited cell proliferation and induced apoptosis. However, silencing all transcripts of APTR had the opposite function to the transcript NR 134251.1. Then we examined the protein level of the proliferation and apoptosis-related genes after silencing the transcript NR 134251.1 of APTR. The results showed that silencing the transcript NR 134251.1 of APTR up-regulated the expression of transcription factor E2F1 and regulated its downstream genes involved in proliferation and apoptosis, including p53, phospho-p53-S392, phospho-p53-T55, p21, Cyclin D1, PUMA, Fas, Bim, BIK, Caspase-3, Caspase-7, and Cyt-c. In conclusion, arsenic induced APTR expression and the transcript NR 134251.1 of APTR have an opposite function to all transcripts, providing a theoretical basis for the prevention and treatment of arsenic exposure. [ABSTRACT FROM AUTHOR]

Simple Summary: Triple-negative breast cancer (TNBC) does not express estrogen or progesterone hormone receptors and does not overexpress the HER2 transmembrane receptor. Treatment of TNBC is challenging due to the lack of these targets for specific therapies. The identification of new targets requires a better understanding of molecular mechanisms underlying the development of TNBC. Here, we show that the embryonic isoform of human RNA polymerase (Pol) III plays an important role in the development and spread of TNBC, as well as in the expression of tumor-specific proteins. Deletion of POLR3G, the specifying subunit of the embryonic isoform of Pol III in a TNBC cell line resulted in reduced tumor growth, suppressed metastasis, and induced expression of transcription factors not present in TNBC but characteristic of other types of breast cancer. Targeting POLR3G expression or processes regulated by POLR3G expression may therefore be useful for the treatment of TNBC in the future. RNA polymerase (Pol) III transcribes short untranslated RNAs that contribute to the regulation of gene expression. Two isoforms of human Pol III have been described that differ by the presence of the POLR3G/RPC32α or POLR3GL/RPC32β subunits. POLR3G was found to be expressed in embryonic stem cells and at least a subset of transformed cells, whereas POLR3GL shows a ubiquitous expression pattern. Here, we demonstrate that POLR3G is specifically overexpressed in clinical samples of triple-negative breast cancer (TNBC) but not in other molecular subtypes of breast cancer. POLR3G KO in the MDA-MB231 TNBC cell line dramatically reduces anchorage-independent growth and invasive capabilities in vitro. In addition, the POLR3G KO impairs tumor growth and metastasis formation of orthotopic xenografts in mice. Moreover, KO of POLR3G induces expression of the pioneer transcription factor FOXA1 and androgen receptor. In contrast, the POLR3G KO neither alters proliferation nor the expression of epithelial–mesenchymal transition marker genes. These data demonstrate that POLR3G expression is required for TNBC tumor growth, invasiveness and dissemination and that its deletion affects triple-negative breast cancer-specific gene expression. [ABSTRACT FROM AUTHOR]

Background: Shenmai injection (SMI), a traditional Chinese medicine (TCM) injection prepared from Red ginseng and Ophiopogon japonicus, is widely used in clinics to treat chemotherapy-induced myelosuppression. Similar to other TCM injections, SMI contains a high amount of carbohydrates (fructose, sucrose, and maltose) in addition to the bioactive substances, specifically ginsenosides (Rg1, Re, and Rb1). To date, the role of these carbohydrates in the hematopoietic function of SMI remains unclear. Purpose: We aimed to investigate the hematopoietic effects and potential mechanisms of SMI and its components, focusing on the carbohydrates present in SMI. Experimental design/methods: First, we evaluated the hematopoietic effect of SMI on 5-fluorouracil (5-FU)-induced myelotoxicity in a tumor-bearing mouse model. Then we prepared mixtures of ginsenosides and carbohydrates according to their proportions in SMI and evaluated their hematopoietic function in mice with 5-FU-induced myelosuppression. Finally, hematopoiesis-related molecular networks were built based on RNA sequencing (RNA-seq) of the bone marrow stromal cells (BMSCs), and the potential mechanisms of carbohydrates and ginsenosides were evaluated. Results: SMI attenuated 5-FU-induced myelotoxicity in tumor-bearing mice. Both ginsenosides and carbohydrates increased the bone marrow nucleated cell (BMNC) count and improved the bone marrow morphology in myelosuppressive mice; they promoted the proliferation of BMSCs derived from those myelosuppressive mice. Bioinformatics analyses revealed ECM-receptor interaction, Hippo signaling, and Wnt signaling are common pathways regulated by both ginsenosides and carbohydrates; Gstt1, Gstp2, Gsta4 and Oplah in Glutathione metabolism pathway and Cd19, Cd79a, and Cd79b in B cell receptor pathway are uniquely regulated genes related to carbohydrates but not ginsenosides. Conclusions: Carbohydrates may collaborate with ginsenosides and contribute to the hematopoietic function of SMI. Carbohydrates could be considered as a bioactive component in this TCM injection. Highlights: Shenmai injection attenuates 5-FU-induced myelotoxicity in tumor-bearing mice. Both carbohydrates and ginsenosides in Shenmai injection promote hematopoiesis. Carbohydrates may regulate Glutathione metabolism and B cell receptor pathway. [ABSTRACT FROM AUTHOR]

Aim: Increasing studies have revealed the participation of lncRNAs in the occurrence and development of cervical cancer. This study explored the influence of lncRNA LINC00649 in cervical cancer. Methods: Expression of LINC00649 and miR‐216a‐3p in cervical cancer was detected by reverse transcription quantitative real‐time polymerase chain reaction (RT‐qPCR). The Kaplan–Meier curve and Cox regression analyses were conducted to evaluate the clinical value of LINC00649 in cervical cancer. The roles of LINC00649 in cervical cancer cells were detected by transfecting siRNA through cellular function assays. Results: LINC00649 expression was increased in cervical cancer tissues, especially in squamous histology, positive lymph node metastasis, and high‐FIGO stage tissues. The higher expression of LINC00649 predicted a shorter survival rate for patients. LINC00649 could bind directly with miR‐216a‐3p. Silence of LINC00649 could enhance the expression of miR‐216a‐3p and suppress the cervical cancer cell proliferation abilities, migration capacities, and invasion power. Whereas, transfection of miR‐216a‐3p inhibitor partially reverses the above cellular activities changes in cervical cancer cells. Conclusions: The LINC00649 expression may act as a prognostic predictor and may aggravate cervical cancer progression by targeting miR‐216a‐3p, providing potential therapeutic targets for patients with cervical cancer. [ABSTRACT FROM AUTHOR]

Allergic rhinitis (AR) is a type I hypersensitivity reaction disease caused by inhaled allergens and immunoglobulin E (IgE)-mediated. Noncoding RNA (ncRNA) is an important regulator involved in gene expression and can be detected in the cytoplasm or extracellular fluid, which mainly includes microRNAs (miRNA, length 22–24 nucleotides), long noncoding RNAs (lncRNA, length >200 nucleotides), and circRNAs. LncRNA and miRNA both participate in the regulation of immune function. Some respiratory viral infections can aggravate allergic rhinitis, such as a respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). However, the interaction between viral infection and allergy is complex and the mechanism is still unclear. In this review, we summarized the interactions of noncoding RNAs and viruses in the occurrence and development of AR, along with the treatments focusing on the noncoding RNAs in the past five years. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been reported to engage in many human diseases, including cardiac hypertrophy. Cardiac hypertrophy was mainly caused by excessive pressure load, which can eventually lead to a decline in myocardial contractility. Gm43843, a novel lncRNA, has not been well explored in cardiac hypertrophy so far. Herein, we are going to search the function and the underlying molecular mechanism of Gm43843 in cardiac hypertrophy. Gm43843 levels were measured via qRT-PCR in mouse myocardial cells when they are treated with angiogenin II (Ang II) or transfected with different plasmids. Western blot assay was implemented to detect the cardiac hypertrophy-related protein markers, while the cell was analyzed via immunofluorescence (IF) assay to evaluate the hypertrophy. Meanwhile, the binding of Gm43843 and the putative targets was examined based on mechanistic assay results. We found that Gm43843 expression was increased with the elevated concentration of Ang II. Inhibited Gm43843 was detected to reduce the hypertrophy of mouse myocardial cells. Meanwhile, Gm43843/miR-153-3p/Cacna1c axis was found to modulate cardiac hypertrophy. In short, Gm43843 promotes cardiac hypertrophy via miR-153-3p/Cacna1c axis. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is one of the most prevalent cancers that often occur in females. Long noncoding RNA differentiation antagonizing nonprotein coding RNA (DANCR) has been involved in the pathogenesis of various tumors, including breast cancer. This study aimed to investigate the role and underlying mechanism of DANCR in breast cancer. Materials and Methods: The level of DANCR was detected in breast cancer tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cell apoptosis was assessed using flow cytometry. Cell migration and invasion were estimated by the Transwell assay. The relationship between DANCR, miR-4319, and vesicle-associated membrane protein-associated protein B (VAPB) was confirmed by bioinformatic analysis and dual-luciferase reporter assay. The level of microRNA-4319 (miR-4319) was tested by qRT-PCR. The expression of VAPB was measured by qRT-PCR or Western blot assay. Results: DANCR and VAPB were upregulated, while miR-4319 was downregulated in breast cancer tissues and cells. Knockdown of DANCR hindered proliferation, migration, and invasion and promoted apoptosis of breast cancer cells. DANCR knockdown inhibited breast cancer development through regulating miR-4319. Inhibition of miR-4319 restrained breast cancer cell progression by targeting VAPB. Moreover, DANCR regulated VAPB expression by sponging miR-4319 in breast cancer cells. Conclusion: DANCR facilitated breast cancer cell progression through regulating the miR-4319/VAPB axis, indicating that DANCR might be a potential biomarker and therapeutic target for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Background: Growing evidence demonstrated that long noncoding RNAs (lncRNAs) were involved in the progression of diverse cancers, including breast cancer (BC). Recent studies indicated that lncRNA nuclear enriched abundant transcript 1 (NEAT1) was overexpressed and facilitated tumor processes in many cancers. Nevertheless, the underlying mechanism of NEAT1 in regulating BC progression is still largely unknown. Materials and Methods: The abundance of NEAT1, microRNA-138-5p (miR-138-5p), and zinc finger protein X-linked (ZFX) was assessed by quantitative real-time polymerase chain reaction. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay were utilized to evaluate cell proliferation, apoptosis, migration, and invasion, respectively. Western blot analysis was applied to detect the protein expression of CyclinD1, Bax, E-cadherin, and ZFX. The interaction between miR-138-5p and NEAT1 or ZFX was predicted by starBase v3.0 and validated by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays. The mice xenograft model was established to investigate the roles of NEAT1 in vivo. Results:NEAT1 was highly expressed and miR-138-5p was lowly expressed in BC tissues and cells. NEAT1 interference or miR-138-5p restoration repressed cell proliferation, migration, and invasion but accelerated apoptosis in BC cells. Moreover, miR-138-5p directly interacted with NEAT1 and its knockdown reversed the suppressive impact of NEAT1 downregulation on the progression of BC cells. In addition, ZFX was a downstream target of miR-138-5p and its upregulation attenuated the antitumor role of miR-138-5p in BC cells. Besides, ZFX expression was positively regulated by NEAT1 and inversely modulated by miR-138-5p. Furthermore, interference of NEAT1 inhibited tumor growth by upregulating miR-138-5p and downregulating ZFX. Conclusion:NEAT1 affected BC progression through modulating miR-138-5p/ZFX axis, providing a vital theoretical basis for BC treatment. [ABSTRACT FROM AUTHOR]

Background: With the promotion of human papillomavirus (HPV) vaccine, cervical cancer has become a current research hotspot, and lncRNA has been confirmed to be used in the research of different diseases. This article systematically expounds the regulation and potential mechanisms of HOXA cluster antisense RNA 3 (HOXA‐AS3) in cervical cancer, and discusses its possibility as a prognostic biomarker for cervical cancer. Methods: Relative expression levels of HOXA‐AS3 and miR‐29a‐3p in tissues and cells were determined by real‐time quantitative polymerase chain reaction (RT‐qPCR). The survival of cervical cancer patients was analyzed by Kaplan–Meier method and the cumulative survival function table was drawn. The proliferation, migration, and invasion levels of HOXA‐AS3 in cells were detected according to cell counting kit‐8 (CCK‐8) and transwell method. The dual‐luciferase reporter gene assay confirmed the mechanism of action between HOXA‐AS3 and miR‐29a‐3p. Results: HOXA‐AS3 was elevated and miR‐29a‐3p was decreased in tissues and cells of cervical cancer patients. Knockdown of HOXA‐AS3 could inhibit the progression of cervical cancer and was more conducive to patient survival. Bioinformatics analysis confirmed that HOXA‐AS3 negatively regulates cervical cancer development by sponging miR‐29a‐3p. Conclusion: In this research, knockdown of HOXA‐AS3 could alleviate the process of cervical cancer by sponging miR‐29a‐3p, suggesting that HOXA‐AS3 may be a potential prognostic target of cervical cancer, which could provide a theoretical basis for future clinical research of cervical cancer. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to identify key genes, non-coding RNAs, and their possible regulatory interactions during gallbladder cancer (GBC). Background: The early detection of GBC, i.e. before metastasis, is restricted by our limited knowledge of molecular markers and mechanism(s) involved during carcinogenesis. Therefore, identifying important disease-associated transcriptome-level alterations can be of clinical importance. Methods: In this study, six NCBI-GEO microarray dataseries of GBC and control tissue samples were analyzed to identify differentially expressed genes (DEGs) and non-coding RNAs {microRNAs (DEmiRNAs) and long non-coding RNAs (DElncRNAs)} with a computational meta-analysis approach. A series of bioinformatic methods were applied to enrich functional pathways, create protein-protein interaction networks, identify hub genes, and screen potential targets of DEmiRNAs and DElncRNAs. Expression and interaction data were consolidated to reveal putative DElncRNAs:DEmiRNAs:DEGs interactions. Results: In total, 351 DEGs (185 downregulated, 166 upregulated), 787 DEmiRNAs (299 downregulated, 488 upregulated), and 7436 DElncRNAs (3127 downregulated, 4309 upregulated) were identified. Eight genes (FGF, CDK1, RPN2, SEC61A1, SOX2, CALR, NGFR, and NCAM) were identified as hub genes. Genes associated with ubiquitin ligase activity, N-linked glycosylation, and blood coagulation were upregulated, while those for cell-cell adhesion, cell differentiation, and surface receptor-linked signaling were downregulated. DEGs-DEmiRNAs-DElncRNAs interaction network identified 46 DElncRNAs to be associated with 28 DEmiRNAs, consecutively regulating 27 DEGs. DEmiRNAs-hsa-miR-26b-5p and hsa-miR-335-5p; and DElnRNAs-LINC00657 and CTB- 89H12.4 regulated the highest number of DEGs and DEmiRNAs, respectively. Conclusion: The current study has identified meaningful transcriptome-level changes and gene-miRNA-lncRNA interactions during GBC and laid a platform for future studies on novel prognostic and diagnostic markers in GBC. [ABSTRACT FROM AUTHOR]

Simple Summary: Long non-coding RNA (lncRNA) is a type of RNA molecule that show striking resemblance to mRNA in terms of synthesis and structure but lacks protein coding capacity. High-throughput RNA-sequencing technologies revealed that they are present in tens of thousands, outnumbering the protein coding genes. Functional investigations over the last two decades reveal that they show highly tissue-, cell type-, and developmental-specific expression and regulate biological processes that control differentiation and development. More importantly, recent evidence suggests that lncRNA are highly dysregulated in cancers and play a crucial role in cancer development and progression through regulating oncogenic and tumor suppressor pathways, cellular metabolism, and the immune response and tumor microenvironment. This article reviews the technologies to identify oncogenesis related lncRNAs and the efforts to understand their functional role in tumor development. We also pay attention towards whether they can serve as potential therapeutic candidates in our fight against cancer. The regulatory nature of long non-coding RNAs (lncRNAs) has been well established in various processes of cellular growth, development, and differentiation. Therefore, it is vital to examine their contribution to cancer development. There are ample examples of lncRNAs whose cellular levels are significantly associated with clinical outcomes. However, whether these non-coding molecules can work as either key drivers or barriers to cancer development remains unknown. The current review aims to discuss some well-characterised lncRNAs in the process of oncogenesis and extrapolate the extent of their decisive contribution to tumour development. We ask if these lncRNAs can independently initiate neoplastic lesions or they always need the modulation of well characterized oncogenes or tumour suppressors to exert their functional properties. Finally, we discuss the emerging genetic approaches and appropriate animal and humanised models that can significantly contribute to the functional dissection of lncRNAs in cancer development and progression. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) has high morbidity and mortality. The interaction between immune cells and tumor cells in the tumor micro-environment is an important factor affecting the tumor progression and prognosis of HNSCC patients. More biomarkers and targets need to be explored to improve patient outcomes. The m6A modification on enhancer RNAs (eRNAs) is associated with the signature of active enhancer, and the function of m6A driving eRNAs in tumor progression has not been reported. In this study, we screened and identified a risk model containing 5 m6A-related eRNA, which can better predict the survival and immunotherapy outcome of patients. The role of m6A-related eRNA in HNSCC cells was verified in vitro. We also combined the risk score and multiple clinical features to construct a nomogram for predicting OS of HNSCC patients, which provides an effective quantitative analysis tool for guiding the personalized precise treatment for patients. At present, the prognostic value of N6-methyladenosine (m6A)-related enhancer RNAs (eRNAs) for head and neck squamous cell carcinoma (HNSCC) still remains unclear. Our study aims to explore the prognostic value of m6A-related eRNAs in HNSCC patients and their potential significance in immune infiltration and immunotherapy. We constructed a 5 m6A-related eRNAs risk model from The Cancer Genome Atlas (TCGA) HNSCC dataset, using univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Based on the SRAMP website and in vitro experiments, it was verified that these 5 m6A-related eRNAs had m6A sites, the expression of which was regulated by corresponding m6A regulators. Moreover, we constructed a nomogram base on 5 m6A-related eRNAs and confirmed the consistency and robustness of an internal TCGA testing set. Further analysis found that the risk score was positively associated with low overall survival (OS), tumor cell metastasis, metabolic reprogramming, low immune surveillance, lower expression of immune-related genes, and higher expression of targeted genes. Finally, we verified that silencing MIR4435-2HG inhibited HNSCC cell migration and invasion. This study contributes to the understanding of the characteristics of m6A-related eRNAs in HNSCC and provides a reference for effective immunotherapy and targeted therapy. [ABSTRACT FROM AUTHOR]

Objective: We aimed to explore the role of long intergenic non‐protein coding RNA 460 (LINC00460) in tongue squamous cell carcinoma (TSCC). Methods: We enrolled 27 TSCC patients to explore LINC00460 expression in clinical TSCC samples. RT‐qPCR measured expression of molecules in this research. Loss‐of‐function assays explored biological function of LINC00460 in TSCC cells. RNA pull‐down assay, luciferase reporter assay, and RIP assay investigated mechanism of LINC00460 underlying TSCC cells. Results: TSCC tissues and cell lines both showed high expression of LINC00460. Functionally, LINC00460 downregulation inhibited TSCC cell growth and promoted TSCC cell apoptosis. Additionally, LINC00460 silencing suppressed tumor growth in vivo. Mechanistically, LINC00460 bound with microRNA 320b (miR‐320b) in TSCC cells. MiR‐320b overexpression suppressed TSCC cell growth and promoted TSCC cell apoptosis. Moreover miR‐320b targeted insulin‐like growth factor 2 mRNA‐binding protein 3 (IGF2BP3) 3′untranslated region in TSCC cells. Furthermore, IGF2BP3 silencing suppressed TSCC cell growth and promoted TSCC cell apoptosis. IGF2BP3 upregulation countervailed effects of silenced LINC00460 on TSCC cells. The LINC00460/miR‐320b/IGF2BP3 axis was associated with lymph node metastasis of TSCC patients. Conclusion: Our research illustrated that LINC00460 facilitated TSCC progression via the miR‐320b/IGF2BP3 axis, highlighting a potential insight for the treatment of TSCC. [ABSTRACT FROM AUTHOR]

This work aims to investigate the effects of tetramethylpyrazine (TMP) on the proliferation, migration, and invasion of glioma cells and to analyze the regulation mechanism of TMP on the long noncoding RNA UBL7-AS1/miR-144-3p pathway. Glioma cell line and normal astrocytes were collected. The expression of UBL7-AS1 was detected by real-time PCR. The glioma cells were overexpressed with UBL7-AS1. CCK-8 and Transwell assays were used to detect cell proliferation and cell invasion ability, respectively. Bioinformatics was adopted to predict the possible regulatory mechanisms of UBL7-AS1. The dual luciferase reporter gene was applied to verify the regulatory effect of RNA UBL7-AS1 with miR-144-3p. TMP inhibited the proliferation and invasion of glioma cells. UBL7-AS1 was highly expressed in glioma tissues and cells. The overexpression of UBL7-AS1 promotes the cell proliferation and invasion of glioma. UBL7-AS1 can act as a sponge for miR-144-3p in glioma cells. The overexpression of UBL7-AS1 can reverse the inhibition of TMP on proliferation, migration, and invasion of glioma cells. TMP inhibits the proliferation, migration, and invasion of glioma cells by regulating the UBL7-AS1/miR-144-3p pathway. [ABSTRACT FROM AUTHOR]

Previous studies have reported that lncRNA PVT1 was closely related to ischemic stroke. Here, the role of PVT1 in ischemic stroke and the underlying mechanism were investigated. OGDR-stimulated PC12 cells were used to construct a cell model to mimic ischemic stroke. si-PVT1, miR-214 mimic, inhibitor, or the negative controls were transfected into PC12 cells prior to OGDR treatment. PVT1, miR-214, and Gpx1 expression was measured by qRT-PCR and western blotting assays. Cell proliferation and apoptosis were tested by CCK-8 assay and western blotting. The expression levels of inflammatory factors were determined by ELISA Kit. Results showed that PVT1 was increased significantly in OGDR PC12 cells. PVT1 knockdown significantly enhanced cell viability and attenuated cell apoptosis, ROS generation, and inflammation in OGDR PC12 cells. More importantly, PVT1 or Gpx1 was a target of miR-214. Mechanistically, PVT1 acted as a competing endogenous RNA of miR-214 to regulate the downstream gene Gpx1. In conclusion, PVT1 knockdown attenuated OGDR PC12 cell injury by modulating miR-214/Gpx1 axis. These findings offer a potential novel strategy for ischemic stroke therapy. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) are sensitive to changing environments and play key roles in health and disease. Emerging evidence indicates that lncRNAs regulate gene expression to shape metabolic processes in response to changing nutritional cues. Here we review various lncRNAs sensitive to fasting, feeding, and high-fat diet in key metabolic tissues (liver, adipose, and muscle), highlighting regulatory mechanisms that trigger expression changes of lncRNAs themselves, and how these lncRNAs regulate gene expression of key metabolic genes in specific cell types or across tissues. Determining how lncRNAs respond to changes in nutrition is critical for our understanding of the complex downstream cascades following dietary changes and can shape how we treat metabolic disease. Furthermore, investigating sex biases that might influence lncRNA-regulated responses will likely reveal contributions toward the observed disparities between the sexes in metabolic diseases. [ABSTRACT FROM AUTHOR]

Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer. Circular RNA hsa_circ_0000144 (circ_0000144) is related to the progression of thyroid cancer. However, the mechanism by which circ_0000144 accelerates PTC progression is still unclear. Circ_0000144 and YWHAH were upregulated in PTC tissues and cells, while miR-1178-3p had an opposite result. Circ_0000144 silencing constrained PTC cell growth in vitro and in vivo and induced apoptosis and repressed migration, invasion, and angiogenesis of PTC cells in vitro. Circ_0000144 acted as a molecular sponge for miR-1178-3p, which targeted YWHAH. MiR-1178-3p inhibitor reversed circ_0000144 silencing-mediated influence on PTC cell malignancy and angiogenesis. Furthermore, YWHAH overexpression overturned miR-1178-3p mimic-mediated influence on malignant behaviors and angiogenesis of PTC cells. Notably, circ_0000144 regulated YWHAH expression by adsorbing miR-1178-3p. Circ_0000144 promoted cell malignancy and angiogenesis by regulating the miR-1178-3p/YWHAH axis in PTC, offering a novel mechanism for the malignancy and angiogenesis of PTC cells. Highlights: Inhibition of circ_0000144 repressed malignant behaviors and angiogenesis of PTC cells in vitro. Knockdown of circ_0000144 constrained PTC cell proliferation in vivo. Circ_0000144 acted as a miR-1178-3p sponge. YWHAH acted as a downstream target for miR-1178-3p. [ABSTRACT FROM AUTHOR]

Background: N6-methyladenosine (m6A) modification plays crucial roles in cancers. However, its alteration in colorectal cancer (CRC) is still poorly described. The purpose of this study is to explore the change of m6A modification and the function of m6A binding protein YTHDC2 in CRC. Methods: The global level of m6A modification was detected by mass spectrometry and dot blotting assay. The expression of YTHDC2 was investigated using The Cancer Genome Atlas and using real-time polymerase chain reaction (RT-qPCR), western blotting, and immunohistochemistry based on CRC tissues. Kaplan–Meier analysis and Cox proportional hazards regression were performed to analyze the prognostic value of YTHDC2. RNA immunoprecipitation (RIP)-seq and m6A immunoprecipitation (MeRIP)-seq were used to explore the direct targets of YTHDC2. Gene oncology (GO) and Gene Set Enrichment Analysis (GSEA) were used to explore the pathways that could be influenced by YTHDC2. Results: No significant difference was observed in the global level of m6A modification on total RNA or mRNA between CRC and adjacent nontumor tissues. We further found a significant decreasing of YTHDC2 in CRC tissues. Kaplan–Meier analysis indicated that lower expression of YTHDC2 was related to the worse disease-free survival and overall survival. In addition, lower expression of YTHDC2 was an independent worse prognostic factor in univariate and multivariate Cox regression analysis. Using YTHDC2-RIP-seq and MeRIP-seq, we identified that YTHDC2 could participate in several important biological signal pathways. Conclusions: In summary, this study suggested that the global level of m6A did not change in CRC and identified that lower YTHDC2 as a prognostic marker for worse survival of CRC. [ABSTRACT FROM AUTHOR]

Noncoding RNA (ncRNA) is a kind of RNA that plays a key role in a variety of biological processes, illnesses, and tumours despite the fact that it cannot be translated into proteins. The HT29 colon cancer cell line was utilized to create a 5-FU drug-resistant cell strain (control group), a lentivirus SNHG20 carrier (OE-SNHG20 group), and an SNHG20 shRNA carrier (SNHG20 shRNA carrier group) (SE-SNHG20 group). To determine the expression of cell SNHG20, a real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was utilized, and cholecystokinin-octapeptide (CCK-8) was used to detect the difference in 5-FU inhibitory concentration 50. The goal of the study was to see how variations in long nonencoding ribonucleic acid (lncRNA) SNHG20 expression affect colon cancer cell 5-fluorouracil (5-FU) chemotherapeutic sensitivity by collecting colon cancer and normal para cancer tissues and analysing the differences in SNHG20 expression. The ability of cell cladogenesis was tested using platform cladogenesis. Cell apoptosis was detected using flow cytometry. Western blots revealed the presence of protein phosphatidylinositol kinase (PI3K), protein kinase B (AKT), caspase-3, e-cadherin, and matrix metalloproteinase 9 (MMP-9) enzymes. The findings revealed that SNHG20 expression was considerably upregulated (P < 0.05) in colon cancer tissue and 5-FU drug-resistant colon cancer cells. Cell 5-FU IC50, cell cladogenesis, cell survival rate, and MMP-9, P-PI3K, and P-AKT expression were all significantly improved. Cell apoptosis and expressions of E-cadherin and caspase-3, on the other hand, were considerably decreased (P < 0.05). Cell 5-FU IC50, cell cladogenesis, cell survival rate, and the expressions of MMP-9, P-PI3K, and P-AKT were all significantly lower in the SE-SNHG20 group, although cell apoptosis and the expressions of E-cadherin and caspase-3 were significantly higher (P < 0.05). The results revealed that lncRNA SNHG20 could inhibit the chemotherapeutic sensitivity of colon cancer cells to 5-FU by regulating PI3K/AKT pathways. The inhibition of lncRNA SNHG20 expression could promote the apoptosis and proliferation of 5-FU-resistant colon cancer cells. [ABSTRACT FROM AUTHOR]