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Background: The imbalance between T helper 17 (Th17) and T regulatory (Treg) cells plays a key role in the progression of multiple myeloma (MM)., Methods: The gene expression profiles of MM were acquired and examined from the Gene Expression Omnibus (GEO) database (GSE72213). Our research involved experimental investigations conducted using the MOPC-MM mouse model. Dysregulation of Treg and Th17 cells was evaluated through flow cytometry, while the levels of inflammatory factors were measured using the enzyme-linked immunosorbent assay. Cell proliferation was gauged using the Cell Counting Kit-8 assay, and cell apoptosis was quantified via flow cytometry. Cell metastasis capabilities were determined by conducting transwell assays. To confirm the relationship between miR-27a and PI3K, a dual-luciferase reporter assay was employed. Finally, proteins associated with the PI3K/AKT/mTOR signaling pathway were assessed using western blotting., Results: MiR-27a exhibited reduced expression levels in MM. Moreover, it exerted control over the equilibrium of Th17 and Treg cells while reducing the expression of inflammatory mediators such as TGF-β1 and IL-10 in an in vivo setting. Elevated miR-27a levels led to the inhibition of cell viability, colony formation capacity, migratory and invasive traits in an in vitro context. The PI3K/AKT/mTOR signaling pathway was identified as a direct target of miR-27a and could reverse the effects induced by miR-27a in MM cells. Notably, PI3K was directly targeted by miR-27a., Conclusions: Our study revealed that miR-27a inhibited MM evolution by regulating the Th17/Treg balance. Inhibition of the PI3K/AKT/mTOR signaling pathway by miR-27a may play a potential mechanistic role., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lu 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.)

The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of neointima formation in vascular restenosis. This study aims to explore the function of the long noncoding RNA H19 in neointima formation. A mouse carotid ligation model was established, and human vascular smooth muscle cells (VSMCs) were used as a cell model. lncRNA H19 overexpression promoted VSMC proliferation and migration. Moreover, miR-125a-3p potentially bound to lncRNA H19, and Fms-like tyrosine kinase-1 (FLT1) might be a direct target of miR-125a-3p in VSMCs. Upregulation of miR-125a-3p alleviated lncRNA H19-enhanced VSMC proliferation and migration. Furthermore, rescue experiments showed that enhanced expression of miR-125a-3p attenuated lncRNA H19-induced FLT1 expression in VSMCs. In addition, the overexpression of lncRNA H19 significantly exacerbated neointima formation in a mouse carotid ligation model. In summary, lncRNA H19 stimulates VSMC proliferation and migration by acting as a competing endogenous RNA (ceRNA) of miR-125a-3p. lncRNA H19 may be a therapeutic target for restenosis.

Background: Circular RNAs (circRNA) are pivotal in hematological diseases. Previous study showed that circ_0014614 (circDAP3) was significantly underexpressed in bone marrow-derived exosomes from essential thrombocythemia (ET) patients, affecting the differentiation of bone marrow lineage cells into megakaryocytes., Methods: Fluorescence in situ hybridization (FISH) was used to display circ_0014614's primary cytoplasmic location in K562 cells. Cytoscape software was used to predict the circRNA-miRNA-mRNA networks, and their expression at the cellular level was detected by Quantitative reverse transcription-polymerase chain reaction (qRT-PCR). qRT-PCR was utilized to detect the expression levels of circ_0014614，miR-138-5p and caspase3 mRNA. Western blot was used to determine the protein levels of GATA-1, RUNX-1, NF-E2, CD41 and caspase3. The proliferation of K562 cells was assessed using the Cell Counting Kit-8 (CCK-8) Assay. Furthermore, the interplay between miR-138-5p and circ_0014614 or caspase3 was elucidated through a Dual-luciferase reporter assay., Results: FISH assay indicated circ_0014614's primary cytoplasmic location in K562 cells. In ET bone marrow and K562 cells, circ_0014614 and caspase3 were down-regulated, whereas miR-138-5p saw a significant surge. Overexpressing circ_0014614 curtailed K562 cells' proliferation and differentiation. Further, circ_0014614 targeted miR-138-5p, with heightened miR-138-5p levels counteracting circ_0014614's inhibition. MiR-138-5p further targeted caspase3, and caspase3 silencing neutralized suppressed miR-138-5p's effects on K562 cell differentiation., Conclusion: Circ_0014614 was down-regulated in ET bone marrow and bone marrow lineage cells, and upregulating circ_0014614 can inhibit bone marrow lineage cells' proliferation and differentiation into megakaryocytes. Mechanistically, circ_0014614 functioned as ceRNA via sponging miR-138-5p and alleviated the inhibitory effect of miR-138-5p on its target caspase3, which potentially deters tumor activity in ET., Competing Interests: Declaration of competing interest The authors declare that there are no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Receptor interacting protein serine/threonine kinase 4 (RIPK4) is widely involved in human cancer development. Nevertheless, its role in colon cancer (COAD) has not been elucidated till now. Our research aimed at exploring the function and underlying molecular mechanism of RIPK4 in COAD progression. Through bioinformatic analyses and RT-qPCR, RIPK4 was discovered to be increased in COAD cells and tissues, and its high level predicted poor prognosis. Loss-of-function assays revealed that RIPK4 silencing suppressed COAD cell growth, induced cell cycle arrest, and enhanced cell apoptosis. In vivo experiments also proved that tumor growth was inhibited by silencing of RIPK4. Luciferase reporter assay validated that RIPK4 was targeted and negatively regulated by miR-575. Western blotting demonstrated that Wnt3a, phosphorylated (p)-GSK-3β, and cytoplasmic and nuclear β-catenin protein levels, β-catenin nuclear translocation, and Cyclin D1, CDK4, Cyclin E, and c-Myc protein levels were reduced by RIPK4 knockdown, which however was reversed by treatment with LiCl, the Wnt/β-catenin pathway activator. LiCl also offset the influence of RIPK4 knockdown on COAD cell growth, cell cycle process, and apoptosis. Finally, RIPK4 downregulation reduced RUNX1 level, which was upregulated in COAD and its high level predicted poor prognosis. RIPK4 is positively associated with RUNX1 in COAD. Overexpressing RUNX1 antagonized the suppression of RIPK4 knockdown on RUNX1, Wnt3a, p-GSK-3β, cytoplasmic β-catenin, nuclear β-catenin, Cyclin D1, CDK4, Cyclin E, and c-Myc levels. Collectively, miR-575/RIPK4 axis repressed COAD progression via inactivating the Wnt/β-catenin pathway through downregulating RUNX1., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In the study, a novel surface-enhanced Raman scattering (SERS)-lateral flow assay (LFA) tray for the real-time detection of pyroptosis-associated miR-155-5p in breast cancer cells was established and validated. The SERS probe modified with monoclonal antibodies and functionalized HP1@5-FAM was first synthesized. When miR-155-5p was present, HP1@5-FAM on the SERS probe specifically recognized target miRNAs and hybridized with them, resulting in HP2 on the T line only capturing some SERS probes that were not bound to miR-155-5p. The T line appeared as a light orange band or there was no color change, and the corresponding Raman detection result showed a weak or insignificant Raman signal. The SERS probe showed high selectivity, satisfactory stability, and excellent reproducibility, and the limit of detection (LOD) for miR-155-5p was 7.26 aM. Finally, the proposed SERS-LFA tray was applied to detect miR-155-5p in MBA-MD-468 cells that underwent varying degrees of pyroptosis, and the detection results of SERS were consistent with those of the conventional real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. The study demonstrated that the SERS-LFA tray was a convenient and ultrasensitive method for miR-155-5p real-time detection, which could provide more detailed information for pyroptosis and be of potential value in guiding the treatment of breast cancer.

Purpose: To explore the function of miR-221-3p in the development and course of chronic periodontitis (CP) and offer a fresh avenue for CP diagnosis and management., Methods: miR-221-3p expression was detected by RT-qPCR. The clinical diagnostic value of miR-221-3p in CP patients was analyzed by receiver operating characteristic (ROC). ELISA was used to determine the IL-1β and IL-6 in CP subjects and healthy controls. Pearson correlation analysis was performed with miR-221-3p. PDLCs were induced by LPS, transfected with miR-221-3p mimics, and their expression was analyzed for the effects of IL-1β, and IL-6., Results: The miR-221-3p expression was lower in the gingival sulcus fluid GCF of CP subjects compared to healthy controls. miR-221-3p showed high potential for clinical diagnosis in CP patients by ROC analysis, with high specificity and sensitivity. miR-221-3p was negatively correlated with Probing pocket depth (PD), Attachment loss (AL), Plaque index (PI), and Bleeding index (BI), and negatively correlated with inflammatory factors IL-1β and IL-6. In LPS-induced PDLCs, IL-1β and IL-6 were significantly increased, whereas miR-221-3p was significantly downregulated. Overexpression of miR-221-3p inhibited the production of inflammatory factors IL-1β and IL-6 in LPS-induced PDLCs., Clinical Significance: miR-221-3p expression may be a potential biological marker for the diagnosis of chronic periodontitis and provide a new direction for its treatment of chronic periodontitis., Competing Interests: The authors declared no conflict of interest. No financial support was received from any organization for the submitted work. Dr. Qi and Dr. Gui contributed equally to the study., (Copyright©American Journal of Dentistry.)

Non-small cell lung cancer (NSCLC) is one of the most common and fatal cancers in the world. Circular RNA (circRNA) can broadly participate in the initiation and progression of the NSCLC. However, the regulatory mechanisms of circRNA in NSCLC remain poorly understood. In present study, we aimed to explore the potential role of circ_0101675 in the progression of NSCLC. Quantitative real-time polymerase chain reaction was performed to examine the expression of circ_0101675, microRNA-607 (miR-607) and programmed cell death receptor ligand 1 (PDL1) in NSCLC tissues and cells. Cell count kit 8 assay, colony formation assay, wound healing assay, transwell assay, tube formation assay and flow cytometry were applied to examine NSCLC cell proliferation, migration, invasion, angiogenesis and apoptosis. NSCLC cells were co-cultured with peripheral blood mononuclear cells to assess immune response. The protein levels of PDL1 and proteins related to apoptosis were detected by western blotting. Dual-luciferase reporter assay and RNA immunoprecipitation assay were conducted to verify the direct target site between miR-607 and circ_0101675 or PDL1. The experiments in vivo were employed to explore the effects of circ_0101675 on tumor growth in NSCLC. Circ_0101675 and PDL1 were high-expressed, while miR-607 was low-expressed in NSCLC cells and cancer tissues. The suppression of circ_0101675 suppressed growth, migration, invasion, angiogenesis and immune escape in NSCLC cells. Mechanistically, we found that high level of circ_0101675 could upregulate PDL1 expression via sponging miR-607. Moreover, the down-regulation of circ_0101675 inhibited the growth of NSCLC tumors in vivo by enhancing miR-607 expression to decrease PDL1 expression. Taken together, our results suggested that circ_0101675 might promote the proliferation, migration, invasion, and immune evasion abilities of NSCLC through miR-607/PDL1 axis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

RNA silencing is an innate immune mechanism of plants against invasion by viral pathogens. Artificial microRNA (amiRNA) can be engineered to specifically induce RNA silencing against viruses in transgenic plants and has great potential for disease control. Here, we describe the development and application of amiRNA-based technology to induce resistance to soybean mosaic virus (SMV), a plant virus with a positive-sense single-stranded RNA genome. We have shown that the amiRNA targeting the SMV P1 coding region has the highest antiviral activity than those targeting other SMV genes in a transient amiRNA expression assay. We transformed the gene encoding the P1-targeting amiRNA and obtained stable transgenic Nicotiana benthamiana lines (amiR-P1-3-1-2-1 and amiR-P1-4-1-2-1). Our results have demonstrated the efficient suppression of SMV infection in the P1-targeting amiRNA transgenic plants in an expression level-dependent manner. In particular, the amiR-P1-3-1-2-1 transgenic plant showed high expression of amiR-P1 and low SMV accumulation after being challenged with SMV. Thus, a transgenic approach utilizing the amiRNA technology appears to be effective in generating resistance to SMV., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: We explored the clinical significance of miR-28-5p pre- and post-endovascular abdominal aortic aneurysm repair (EVAR) in abdominal aortic aneurysm (AAA) patients., Methods: Subjects included AAA patients receiving EVAR and non-AAA people without statistical differences from AAA patient in comorbidities/Framingham risk score. Fasting elbow venous blood (4 mL) was collected in the morning of the day of EVAR surgery and in the morning of 3 months post-EVAR. Pre-/post-EVAR serum miR-28-5p expression, AAA maximum diameter alterations, CD 3+ /CD 4+ /CD 8+ /TC/TG pre-/post-EVAR, and the correlations between miR-28-5p and AAA maximum diameter were investigated. Prediction of miR-28-5p on post-EVAR mortality, prognosis, and independent factors of post-EVAR death were analyzed using receiver operating characteristic curve (ROC)/Kaplan-Meier curve/univariable and multivariable Cox regression. According to the cut-off value of ROC curve for postoperative miR-28-5p was the cut-off value, and the patients were classified into the miR-28-5p high- and low-expression groups. The survival or death of both groups were compared after 48-month follow-up., Results: Serum miR-28-5p levels in AAA patients dropped post-EVAR. AAA patients showed notable differences in CD 3+ /CD 4+ /CD 8+ /TC/TG levels pre-/post-EVAR. The miR-28-5p low-expression group exhibited higher CD 3+ /CD 4+ and lower CD 8+ /TC/TG levels. We observed a positive correlation between post-EVAR miR-28-5p and AAA maximum diameter and between the pre-/post-EVAR miR-28-5p fold change and the AAA maximum diameter change. Postoperative miR-28-5p demonstrated good predictive value for postoperative death. Hypertension, Framingham risk score, TC, TG, and miR-28-5p were independent influencing factors of post-EVAR death., Conclusion: EVAR decreased serum miR-28-5p expression in AAA patients. Post-operative miR-28-5p level and pre-/post-operative fold change level are positively-correlated with AAA diameter., (© 2024. The Author(s).)

Background: Endoplasmic reticulum (ER) stress and oxidative stress are the major pathologies encountered after intracerebral hemorrhage (ICH). Inositol-requiring enzyme-1 alpha (IRE1α) is the most evolutionarily conserved ER stress sensor, which plays a role in monitoring and responding to the accumulation of unfolded/misfolded proteins in the ER lumen. Recent studies have shown that ER stress is profoundly related to oxidative stress in physiological or pathological conditions. The purpose of this study was to investigate the role of IRE1α in oxidative stress and the potential mechanism., Methods: A mouse model of ICH was established by autologous blood injection. The IRE1α phosphokinase inhibitor KIRA6 was administrated intranasally at 1 h after ICH, antagomiR-25 and agomiR-25 were injected intraventricularly at 24 h before ICH. Western blot analysis, RT-qPCR, immunofluorescence staining, hematoma volume, neurobehavioral tests, dihydroethidium (DHE) staining, H 2 O 2 content, brain water content, body weight, Hematoxylin and Eosin (HE) staining, Nissl staining, Morris Water Maze (MWM) and Elevated Plus Maze (EPM) were performed., Results: Endogenous phosphorylated IRE1α (p-IRE1α), miR-25-3p, and Nox4 were increased in the ICH model. Administration of KIRA6 downregulated miR-25-3p expression, upregulated Nox4 expression, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, reduced body weight, aggravated spatial learning and memory deficits, and increased anxiety levels. Then antagomiR-25 further upregulated the expression of Nox4, promoted the level of oxidative stress, increased hematoma volume, exacerbated brain edema and neurological deficits, whereas agomiR-25 reversed the effects promoted by KIRA6., Conclusion: The IRE1α phosphokinase activity is involved in the oxidative stress response through miR-25/Nox4 pathway in the mouse ICH brain., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

It is metabolic and signaling crosstalk between stromal cells and tumors in the tumor microenvironment, which influences several aspects of tumor formation and drug resistance, including metabolic reprogramming. Despite considerable findings linking lncRNAs in HIF-1-related regulatory networks to cancer cell, little emphasis has been given to the role in communication between cancer-associated fibroblasts (CAFs) and tumor cells. Previously, we observed that NNT-AS1 was substantially expressed in CAFs cells and CAFs exosomes, and subsequently investigated the influence of CAFs exosomal NNT-AS1 on glucose metabolism, proliferation, and metastasis of pancreatic ductal adenocarcinoma (PDAC) cells. Transmission electron microscopy was used to examine exosomes secreted by PDAC patient-derived CAFs. qRT-PCR was used to evaluate the expression of NNT-AS1, miR-889-3p, and HIF-1. The role of CAFs-derived exosomal NNT-AS1 in PDAC cell progression and metabolism have been identified. Dual luciferase reporter assays examined the binding between NNT-AS1, miR-889-3p, and HIF-1. After PDAC cells co-culture exosomes secreted by CAFs, we found that they alter glucose metabolism, proliferation, and metastasis. In PDAC cells, CAF-derived exosomal lncRNA NNT-AS1 acted as a molecular sponge for miR-889-3p. Furthermore, HIF-1 could be targeted by miR-889-3p and was controlled by NNT-AS1. This study explores the mechanism by which NNT-AS1 influences the interaction of CAFs on glycolytic remodeling, proliferation, and metastasis of tumor cells through regulating miR-889-3p/HIF-1α, which also helps discover new clinical treatment targets for PDAC., (© 2024. The Author(s).)

Overexposure to manganese (Mn) can lead to neurotoxicity, the underlying mechanisms remain incompletely understood. Circular RNAs (circRNAs) have emerged as important regulators in various biological processes. It is plausible that circRNAs may be involved in the biological mechanisms underlying Mn caused neurotoxicity. Here, circRest was downregulated in Mn-exposed mouse neuroblastoma cells (N2a cells) by RNA sequencing and quantitative real-time PCR. When circRest was overexpressed, it led to an increase in cell viability and a decrease in apoptosis following Mn exposure. Conversely, silencing circRest resulted in opposite effects in N2a cells. Further investigation revealed that circRest acts as a mmu-miR-6914-5p sponge, and mmu-miR-6914-5p could bind and inhibit Ephb3, thereby promoting apoptosis in N2a cells. This was confirmed through RNA antisense purification and dual luciferase reporter assays. Additionally, the circRest/mmu-miR-6914-5p/Ephb3 axis may influence memory and learning in mice following Mn exposure. In conclusion, our study uncovers a novel mechanism by which circRest may attenuate Mn caused neurotoxicity via the mmu-miR-6914-5p/Ephb3 axis., 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 Ltd.)

The expression of microRNA (miRNA) changes in many diseases plays an important role in the diagnosis, treatment, and prognosis of diseases. Spinal cord injury (SCI) is a serious disease of the central nervous system, accompanied by inflammation, cell apoptosis, neuronal necrosis, axonal rupture, demyelination, and other pathological processes, resulting in impaired sensory and motor functions of patients. Studies have shown that miRNA expression has changed after SCI, and miRNAs participate in the pathophysiological process and treatment of SCI. Therefore, quantitative analysis and monitoring of the expression of miRNA were of great significance for the diagnosis and treatment of SCI. Through the SCI-related miRNA chord plot, we screened out miRNA-21-5p and miRNA-let-7a with a higher correlation. However, for traditional detection strategies, it is still a great challenge to achieve a fast, accurate, and sensitive detection of miRNA in complex biological environments. The most frequently used method for detecting miRNAs is polymerase chain reaction (PCR), but it has disadvantages such as being time-consuming and cumbersome. In this paper, a novel SERS sensor for the quantitative detection of miRNA-21-5p and miRNA-let-7a in serum and cerebrospinal fluid (CSF) was developed. The SERS probe eventually formed a sandwich-like structure of Fe 3 O 4 @hpDNA@miRNA@hpDNA@GNCs with target miRNAs, which had high specificity and stability. This SERS sensor achieved a wide range of detection from 1 fM to 1 nM and had a good linear relationship. The limits of detection (LOD) for miRNA-21-5p and miRNA-let-7a were 0.015 and 0.011 fM, respectively. This new strategy realized quantitative detection and long-term monitoring of miRNA-21-5p and miRNA-let-7a in vivo. It is expected to become a powerful biomolecule analysis tool and will provide ideas for the diagnosis and treatment of many diseases.

Studying the regulatory mechanism of gastric disease progression to gastric cancer (GC) is essential. miR-520f expression is down-regulated in GC and inhibits the proliferation of gastric cancer cells, suggesting that it is associated with the development of GC, but whether it plays a role in the gastric precancerous lesion (GPL) is unclear. This study aimed to investigate the effect of miR-520f-3p in the N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced GPL model and to elucidate the role of its downstream target gene Kruppel-like factor 7 (KLF7) in it. The experimental results showed that miR-520f-3p expression was down-regulated in the MNNG-induced GES-1 cell model, and overexpression of miR-520f-3p reversed the effects of MNNG on cell migration, invasion and epithelial-mesenchymal transition (EMT) -related protein expression. Meanwhile, overexpression of KLF7 attenuated the effect of miR-520f-3p on GPL. In a mouse GPL model, it was observed that MNNG elicited inflammation and EMT processes in mouse gastric tissues through the KLF7/ Nuclear Factor Kappa B (NFκB) pathway, and silencing KLF7 alleviated MNNG-induced gastric epithelial cell injury and gastric atrophy symptoms. These results provide a new perspective for understanding the development of GPL, and the development of new therapies targeting miR-520f-3p and KLF7 may provide new ideas for the prevention and treatment of gastric 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 B.V. All rights reserved.)

The role of long intergenic noncoding RNA 00893 (Linc00893) in asthenozoospermia (AS) and its impact on sperm motility remains unclear The present study explored the effect of Linc00893 on AS, specifically its effect on sperm motility and its relationship with spermatogonial stem cell (SSC) vitality and myosin heavy chain 9 (MYH9) protein expression. Linc00893 expression was analyzed in semen samples using reverse transcription‑quantitative PCR, revealing a significant downregulation in samples from individuals with AS compared with those from healthy subjects. This downregulation was found to be negatively correlated with parameters of sperm motility. To further understand the role of Linc00893, small interfering RNA was used to knockdown its expression in SSCs. This knockdown led to a marked decrease in cell vitality and an increase in apoptosis. Notably, Linc00893 knockdown was shown to inhibit MYH9 expression by competitively binding with microRNA‑107, a finding verified by dual‑luciferase reporter and RNA immunoprecipitation assays. Furthermore, using the GSE160749 dataset from the Gene Expression Omnibus database, it was revealed that MYH9 protein expression was downregulated in AS samples. Subsequently, lentiviral vectors were constructed to induce overexpression of MYH9, which in turn reduced SSC apoptosis and counteracted the apoptosis triggered by Linc00893 knockdown. In conclusion, the present study identified the role of Linc00893 in AS, particularly its regulatory impact on sperm motility, SSC vitality and MYH9 expression. These findings may provide information on the potential regulatory mechanisms in AS development, and identify Linc00893 and MYH9 as possible targets for diagnosing and treating AS‑related disorders.

Acute myeloid leukemia (AML) is a highly heterogeneous malignant disease of the blood cell. The current therapies for AML are unsatisfactory and the molecular mechanisms underlying AML are unclear. 5-methylcytosine (m5C) is an important posttranscriptional modification of mRNA, and is involved in the regulation of mRNA stability, translation, and other aspects of RNA metabolism. However, based on our knowledge of published literature, the role of the m5C regulators has not been explored in AML till date. In this study, we clarified the expression and gene variants of m5C regulators in AML and found that most m5C regulators were differentially expressed and correlated with disease prognosis. We also found that the methylation status of certain m5C regulators (e.g., DNMT3A , DNMT3B ) affects the survival of AML patients. Two m5C modification subtypes, and high- and low-risk subgroups identified based on the expression of m5C regulators showed significant differences in the prognosis as well as immune cell infiltration. In addition, most of the m5C regulators were found to be correlated with miRNA expression in AML, as well as IC50 values of many drugs. The miRNA and GSVA analysis were used to identify the different miRNAs and KEGG or hallmark pathways between high- and low-risk subgroups. We also built a prognostic model based on m5C regulators, which was validated by two GSE databases. To verify the reliability of our analysis and conclusions, qPCR was used to identify the expressions of m5C regulators between normal and AML. In summary, we comprehensively explored the molecular characteristics of m5C regulators and built a prognostic model in AML. We proposed new mechanistic insights into the role of m5C in multiple databases and clinical data, which may pave novel ways for the development of therapeutic strategies.

Glioma cell sensitivity to temozolomide (TMZ) is critical for effective treatment and correlates with patient survival, although mechanisms underlying this activity are unclear. Here, we reveal a new mechanism used by glioma cells to modulate TMZ sensitivity via regulation of SORBS2 and DDR1 genes by super-enhancer RNA LINC02454. We report that LINC02454 activity increases glioma cell TMZ sensitivity by maintaining long-range chromatin interactions between SORBS2 and the LINC02454 enhancer. By contrast, LINC02454 activity also decreased glioma cell TMZ sensitivity by promoting DDR1 expression. Our study suggests a bivalent function for super-enhancer RNA LINC02454 in regulating glioma cell sensitivity to TMZ., (© 2024. The Author(s).)

Circular RNA (circRNA) was an important modulator and potential molecular target of nonsmall cell lung cancer (NSCLC). CircSATB2 was reported to be upregulated in NSCLC. However, the role and mechanism of circSATB2 in NSCLC progression remain to be illustrated. The RNA and protein expression was detected by quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry assay. Cell counting kit-8, cell colony formation, and 5-ethynyl-2'-deoxyuridine assays were applied to assess cell growth. The migrated and invaded cells were examined by transwell assay. Flow cytometry was performed to measure apoptotic cells. The interaction among circSATB2, microRNA-150-5p (miR-150-5p), and tripartite motif-containing protein 66 (TRIM66) was identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. An in vivo experiment was conducted to investigate the effect of circSATB2 on tumor growth. CircSATB2 expression was highly expressed in NSCLC tissues and cell lines. CircSATB2 and TRIM66 silencing both suppressed NSCLC cell growth, migration, and invasion whereas promoted NSCLC cell apoptosis. CircSATB2 acted as a molecular sponge for miR-150-5p, and miR-150-5p interacted with the 3' untranslated region (3'UTR) of TRIM66. Moreover, circSATB2 knockdown-induced effects were partly reversed by TRIM66 overexpression in NSCLC cells. Besides, cirSATB2 expression was negatively correlated with miR-150-5p level and positively correlated with TRIM66 level in NSCLC tumor tissues. CircSATB2 knockdown blocked xenograft tumor growth in vivo. In summary, this study verified that circSATB2 stimulated NSCLC cell malignant behaviors by miR-150-5p/TRIM66 pathway, providing a possible circRNA-targeted therapy for NSCLC., (© 2023 Wiley Periodicals LLC.)

Background and Aims: The traditional treatment of diabetic wounds is unsatisfactory. Exosomes isolated from bone marrow mesenchymal stem cells (BMSCs) promote the healing of diabetic wounds. However, whether the exosomes secreted by interferon (IFN)-γ-pretreated BMSCs have an enhanced therapeutic effect on diabetic wound healing and the relevant mechanisms remain unclear., Methods: In this study, we isolated exosomes from the corresponding supernatants of BMSCs with (IExos) or without IFN-γ treatment (NExos). Human umbilical vein endothelial cells (HUVECs) were used to investigate the proliferation, migration, and tube formation under different treatments in vitro. Diabetic mice were induced by intraperitoneal administration of streptozotocin, and a circular full-thickness dermal defect was then made on the back of each mouse, followed by a multisite subcutaneous injection of phosphate buffered saline or exosomes. Hematoxylin-eosin (H&E) staining, Masson's trichrome staining, and histological analysis were performed to assess the speed and quality of wound healing., Results: NExos treatment accelerated the healing of diabetic wounds by promoting angiogenesis in vivo and in vitro, and IExos exhibited superior therapeutic efficiency. MicroRNA (miR)-126-3p was significantly increased in IExos, and exosomal miR-126-3p promoted angiogenesis and diabetic wound healing via its transfer to HUVECs. miR-126-3p regulates SPRED1 by directly targeting the 3'-UTR. Mechanistically, IFN-γ-pretreated BMSCs secreted miR-126-3p-enriched exosomes, which enhanced the function of HUVECs and promoted angiogenesis via the SPRED1/Ras/Erk pathway., Conclusion: Exosomal miR-126-3p secreted from IFN-γ-pretreated BMSCs exhibited higher therapeutic efficacy than NExos in diabetic wound healing by promoting angiogenesis via the SPRED1/Ras/Erk axis., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background: Myocardial ischemia-reperfusion (I/R), a harmful process in the treatment of cardiovascular diseases, can cause secondary damage to the cardiac tissues. Circular RNAs (circRNAs) are important regulators in a number of cardiac disorders. However, the role of circHDAC9 in myocardial I/R injury has not been clarified., Methods: Human cardiac myocytes (HCMs) were treated with hypoxia/reoxygenation (H/R) and mice were subjected to I/R. Quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to analyze the expression of circHDAC9, miR-671-5p, and SOX4, and western blot was used to detect SOX4 protein. The binding relationship among circHDAC9, miR-671-5p, and SOX4 was confirmed by RNA pull-down, luciferase, and RNA immunoprecipitation (RIP) assays. The effects of circHDAC9/miR-671-5p/SOX4 axis on the apoptosis, oxidative stress and inflammation were evaluated in both myocardial I/R injury models., Results: The expression of circHDAC9 and SOX4 was noticeably elevated, whereas miR-671-5p expression was downregulated in both myocardial I/R injury models. circHDAC9 knockdown significantly reduced the apoptosis, activities of caspase-3 and caspase-9, ROS intensity, MDA activity, and concentrations of TNF-α, IL-1β, and IL-6, but increased the viability and SOD activity in H/R-treated HCMs. Suppression of circHDAC9 dramatically reduced the levels of circHDAC9 and SOX4, while enhanced miR-671-5p expression in H/R-treated HCMs. CircHDAC9 functioned via sponging miR-671-5p to regulate SOX4 expression in vitro. Additionally, silencing of circHDAC9 improved the pathological abnormalities and cardiac dysfunction, and reduced the apoptosis, oxidative stress and inflammation in mice with myocardial I/R injury., Conclusions: Inhibition of circHDAC9 significantly improved myocardial I/R injury by regulating miR-671-5p/SOX4 signaling pathway., Competing Interests: Declaration of Competing Interest The authors assert no competing financial interests., (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Current studies have suggested that miRNA is beneficial in inhibiting myocardial remodeling after myocardial infarction (AMI), however, its underlying mechanism is unclear., Objectives: We aimed to investigate whether miR-150 can inhibit myocardial remodeling after myocardial infarction and whether this process is regulated by the miR-150/TET3 pathway., Methods: On the first day, C57BL/6 AMI mice(n = 15) were administrated with miR-150, and another 15 AMI mice were administrated with the same volume of control Agomir. Left ventricular ejection fraction (LVEF%) and myocardial remodeling were compared after one week; TET3 (ten-eleven translocation 3) and VEGF-α (vascular endothelial growth factor-α) were also determined in the infracted heart simultaneously. The neovascularization in the infarcted area at day 21 was compared through CD31 using fluorescence microscopy; Activated monocytes stimulated with LPS were transfected with miR-150. Laser scanning confocal microscopy was used to detect the intracytoplasmic imaging of miR-150 in Ly6C high monocytes. Expression of the miR-150 in the monocytes was measured using Q-PCR. After 48 h, the proportion of Ly6C high/low monocytes was determined using flow cytometry. Expression of TET3 in Ly6C high/low monocytes was measured using Q-PCR and Western blot. After the downregulation of TET3 specifically, the levels of Ly6C high/low monocytes were further determined., Results: We first observed an increased trend of mice survival rate in the miR-150 injection group, but it didn't reach a statistical difference (66.7% vs. 40.0%, p = 0.272). However, AMI mice administrated with miR-150 displayed better LVEF% (51.78%±2.90% vs. 40.28%±4.20%, p<0.001) and decreased infarct size% (25.47 ± 7.75 vs. 50.39 ± 16.91, p = 0.002). After miR-150 was transfected into monocytes, the percentage of Ly6C low monocytes increased significantly after 48 h (48.5%±10.1% vs. 42.5%±8.3%, p < 0.001). Finally, Western blot analysis (0.56 ± 0.10/β-actin vs. 0.99 ± 0.12/β-actin, p < 0.001) and real-time PCR (1.09 ± 0.09/GAPDH vs. 2.53 ± 0.15/GAPDH, p < 0.001, p < 0.001) both confirmed decreased expression of TET3 in monocytes after transfection with miR-150. After the downregulation of TET3 specifically, Ly6C low monocytes showed a significant increase (16.73%±6.45% vs. 6.94%±2.99%, p<0.001, p < 0.001)., Conclusions: miR-150 alleviated myocardial remodeling after AMI. Possible mechanisms are ascribed to the regulating of TET3 and VEGF-α in inflammatory monocytes., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

The therapeutic role of tendon stem cells (TSCs) in tendon-related injuries has been well documented. Small extracellular vesicles (sEVs) are being increasingly used as new biotherapeutic agents for various diseases. Therefore, the potential function of TSC-sEVs in tendon injury repair warrants further investigation. In this study, we explored the effects of TSC-sEVs on TSC proliferation, migration, and differentiation in vitro in an autocrine manner. We further used a novel exosomal topical treatment with TSC-sEVs loaded with gelatin methacryloyl (GelMA) hydrogel in vivo; we mixed sufficient amounts of TSC-sEVs with GelMA hydrogel to cover the damaged molded Achilles tendon tissue and then exposed them to UV irradiation for coagulation. GelMA loading ensured that TSC-sEVs were slowly released at the injury site over a long period, thereby achieving their full local therapeutic effects. Treatment with TSC-sEVs loaded with GelMA significantly improved the histological score of the regenerated tendon by increasing the tendon expression while inhibiting the formation of excessive ossification and improving the mechanical properties of the tissue. Moreover, miRNA sequencing in TSC-sEVs, TSCs, and TSCs receiving sEVs revealed that TSC-sEVs altered the miRNA expression profile of TSCs, with increased expression of miR-145-3p. In conclusion, our study demonstrates that TSC-sEVs can play a key role in treating tendon injuries and that loading them with GelMA can enhance their effect in vivo. Moreover, miR-145-3p has a major functional role in the effect of TSC-sEVs. This study offers new therapeutic ideas for the local treatment of Achilles tendon injuries using sEVs. STATEMENT OF SIGNIFICANCE: In this study, we demonstrated that TSC-sEVs play a key role in treating tendon injuries and that loading them with GelMA hydrogel can act as a fixation and slow release in vivo. Moreover, it identifies the major functional role of miR-145-3p in the effect of TSCs that were identified and validated by miRNA sequencing. Our study provides a basis for further research on GelMA slow-release assays that have potential clinical applications. It offers new therapeutic ideas for the local treatment of Achilles tendon injuries using TSC-sEVs., 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 © 2023 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: MicroRNA-424 (MiR-424) is proved to be a tumor suppressor against many malignancies, including hepatocellular carcinoma (HCC). Nevertheless, its role in diagnosing HCC remained poorly understood. The authors' research investigated diagnostic value of serum miR-424 in HCC. Materials and Methods: Relative expression levels of serum miR-424 in HCC patients and healthy individuals were measured via quantitative real-time polymerase chain reaction. χ 2 test was applied to analyze the correlation between miR-424 expression and clinical features of HCC cases. Diagnostic value was estimated via plotting a receiver operating characteristic (ROC) curve. Results: Serum miR-424 expression was obviously downregulated in HCC cases in comparison to healthy persons ( p  < 0.001). miR-424 expression presented strong correlation with tumor node metastasis stage ( p  = 0.022), Barcelona Clinic Liver Cancer stage ( p  < 0.001), metastasis ( p  = 0.037), and vein invasion ( p  = 0.033). ROC curve analysis manifested an area under the curve of 0.768 with a sensitivity of 75.0% and a specificity of 72.4%, suggesting that serum miR-424 had high diagnostic value in HCC patients. Conclusions: The data suggest that serum miR-424 may represent a biomarker in early detection of HCC.

Melatonin has been proved to be involved in testosterone synthesis, but whether melatonin participates in testosterone synthesis by regulating miRNA in Leydig cells is still unclear. The purpose of this study is to clarify the mechanism of melatonin on Leydig cells testosterone synthesis from the perspective of miRNA. Our results showed that melatonin could significantly inhibit testosterone synthesis in rooster Leydig cells. miR-7481-3p and CXCL14 were selected as the target of melatonin based on RNA-seq and miRNA sequencing. The results of dual-luciferase reporter assays showed that miR-7481-3p targeted the 3'-UTR of CXCL14 . The overexpression of miR-7481-3p significantly inhibited the expression of CXCL14 and restored the inhibitory role of melatonin testosterone synthesis and the expression of StAR, CYP11A1, and 3β-HSD in rooster Leydig cells. Similarly, interference with CXCL14 could reverse the inhibitory effect of melatonin on the level of testosterone synthesis and the expression of StAR, CYP11A1, and 3β-HSD in rooster Leydig cells. The RNA-seq results showed that melatonin could activate the PI3K/AKT signal pathway. Interference with CXCL14 significantly inhibited the phosphorylation level of PI3K and AKT, and the inhibited PI3K/AKT signal pathway could reverse the inhibitory effect of CXCL14 on testosterone synthesis and the expression of StAR, CYP11A1 and 3β-HSD in rooster Leydig cells. Our results indicated that melatonin inhibits testosterone synthesis by targeting miR-7481-3p/ CXCL14 and inhibiting the PI3K/AKT pathway.

Cancer stemness and osteosarcoma (OS) malignant progression are closely associated. However, the molecular mechanisms underlying this association have not been fully demonstrated. Long noncoding RNAs (lncRNAs) are an intriguing class of widely prevalent endogenous RNAs involved in OS progression, the vast majority of which have not been characterized functionally. Here, we identified tumor promoter lncRNA WAC-AS1 to be highly expressed in OS tumors and associated with worse survival. Further analysis revealed that WAC-AS1 increased tumorsphere formation of OS cells and promoted metastasis, as confirmed by cell proliferation, transwell and wound healing assays. MiR-5047 was identified as a downstream target of WAC-AS1. Subsequently, based on bioinformatics analysis, RIP assay and luciferase reporter assay, SOX2 mRNA was verified as a target of miR-5047. WAC-AS1 enhanced OS cell proliferation and stemness via acting as a ceRNA by binding to miR-5047, thereby increasing SOX2 expression. In addition, SOX2 bound to the promoter region of WAC-AS1 and promoted its transcription, thereby forming a positive feedback loop to regulate OS malignancy. Taken together, our findings show WAC-AS1 is a tumor promoter and a key regulator of OS cell stemness and metastasis via a miR-5047/SOX2 axis., (© 2023. The Author(s).)

Colorectal cancer (CRC) is a malignant tumor with high morbidity and mortality. It is well-accepted that dysregulated lncRNAs are closely related to the development of CRC. In this study, the function and mechanism of RNASEH1-AS1 in CRC were investigated. RT-qPCR and western blot detected the expression of targeted genes in tissues and cells. CCK-8, clone formation, wound healing assay, and Transwell were applied to evaluate CRC cell malignant behaviors. ChIP, RIP, and RNA pull-down validated interactions among RNASEH1-AS1, H3K27ac, CBP, BUD13, and ANXA2. Nucleoplasmic separation and FISH assay determined the location of RNASEH1-AS1 in CRC cells. IHC assay was used to detect Ki-67 expression in tumor tissues from mice. RNASEH1-AS1 was highly expressed in CRC tumor tissues and cells. RNASEH1-AS1 silencing effectively suppressed the viability, proliferation, migration, and invasion of CRC cells. In addition, CBP-mediated H3K27ac increased RNASEH1-AS1 expression in CRC cells and RNASEH1-AS1 could elevate ANXA2 expression through recruiting BUD13. Furthermore, RNASEH1-AS1 silencing inhibited malignant phenotypes of CRC cells and tumor growth in mice through decreasing ANXA2 expression and inactivating the Wnt/β-catenin pathway. Our results revealed that RNASEH1-AS1 induced by CBP-mediated H3K27ac activated Wnt/β-catenin pathway to promote CRC progression through recruiting BUD13 to stabilize ANXA2 mRNA, which provides substantial evidence of RNASEH1-AS1 in CRC. Targeting RNASEH1-AS1 might alleviate CRC progression.

Chemotherapy-induced neuropathic pain (CINP) is a dose-limiting adverse event affecting 40% of chemotherapy patients. MiRNA-mRNA interaction plays an important role in various processes. However, detailed profiling of miRNA-mRNA interactions in CINP remains unclear. Here, a rat-based CINP model was established using paclitaxel, followed by nociceptive behavioral tests related to mechanical allodynia, thermal hyperalgesia, and cold allodynia. The landscape of miRNA-mRNA interaction in the spinal dorsal horn was investigated through mRNA transcriptomics and small RNA sequencing. Under CINP condition, 86 differentially expressed mRNAs and 56 miRNAs were identified. Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated the activity of Odorant binding, postsynaptic specialization and synaptic density, extracellular matrix, mitochondrial matrix, retrograde endocannabinoid signaling, and GTPase activity. Protein-protein interaction (PPI), networks of circRNA-miRNA-mRNA, lncRNA-miRNA-mRNA, and TF-genes were demonstrated. We next explored the immune infiltration microenvironment and found a higher infiltration abundance of Th17 and a lower abundance of MDSC in CINP. RT-qPCR and dual-luciferase assays were used to verify the sequencing results, and single-cell analysis based on the SekSeeq database was conducted. Combined with bioinformatics analyses and experimental validations, Mpz, a protein-coding gene specifically expressed in Schwann cells, was found critical in maintaining CINP under miRNA regulation. Therefore, these data highlight the expression patterns of miRNA-mRNA, and the underlying mechanism in the spinal dorsal horn under CINP condition, and Mpz may serve as a promising therapeutic target for patients with CINP., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Polycystic ovary syndrome (PCOS) is a perplexing condition in females of reproductive age. Dysplasia of ovarian granulosa cell (GC) is implicated in PCOS. Follicular fluid (FF)-extracellular vesicles (Evs) are important in cell-cell communication during follicular development. The current study elaborated on the function and mechanism of FF-Evs in the viability and apoptosis of GC cells in PCOS development. Human GC cells KGN were treated with dehydroepiandrosterone (DHEA) to mimic a PCOS-like condition in vitro, which were further co-cultured with the FF-derived Evs (FF-Evs). The FF-Evs treatment significantly reduced DHEA-induced apoptosis of KGN cells while promoting cell viability and migration. The lncRNA microarray analysis showed that FF-Evs mainly deliver LINC00092 into the KGN cells. Knockdown of LINC00092 negated the protective effect of FF-Evs against DHEA-induced damage on KGN cells. Moreover, by performing bioinformatics analyses and biotin-labeled RNA pull-down assay, we found that LINC00092 could bind to the RNA binding protein LIN28B and inhibit its binding to pre-microRNA-18-5p, which allowed biogenesis of pre-miR-18-5p and increased the expression of miR-18b-5p, a miRNA with known alleviating role in PCOS by suppressing the PTEN mRNA. Collectively, the present work demonstrates that FF-Evs can alleviate DHEA-induced GC damage by delivering LINC00092., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: MicroRNA-19b (miR-19b) has been reported to be downregulated in polycystic ovary syndrome (PCOS), while its upstream regulators are unclear. We speculated that miR-19b could potentially form a binding relationship with BBOX1 antisense RNA 1 (BBOX1-AS1), a long non-coding RNA recognized for its critical role in ovarian cancer. Subsequently, we investigated into their interaction in PCOS., Methods: The expression of miR-19b and BBOX1-AS1 in follicular fluid from both control women (n = 80) and women with PCOS (n = 80) was detected by RT-qPCR. Correlations were analyzed with Pearson' correlation coefficient. The binding of miR-19b to the wild-type (-wt) ad mutant (-mut) BBOX1-AS1 was determined by RNA-RNA pulldown assay. Their interactions were detected by overexpression assay. Bromodeoxyuridine (BrdU) assay was applied for proliferation analysis., Results: BBOX1-AS1 was highly upregulated, while miR-19b was downregulated in PCOS. There was no close correlation across PCOS and the control samples. Consistently, they did not regulate the expression of each other in granulosa cells. However, BBOX1-AS1-wt, but not BBOX1-AS1-mut, could directly interact with miR-19b. BBOX1-AS1 suppressed the role of miR-19b in inhibiting granulosa cell proliferation., Conclusion: BBOX1-AS1 is highly upregulated in PCOS, and it may serve as an endogenous competing RNA for miR-19b to suppress its role in inhibiting granulosa cell proliferation. Our study suggested the role of BBOX1-AS1 as a potential target to treat PCOS., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objectives: To investigate the role and mechanism of circRNA-SR-related CTD associated factor 8 (SCAF8) in regulating endothelial cell pyroptosis in high glucose environment., Methods: Human umbilical vein endothelial cells (HUVECs) were cultured and divided into six groups. The normal control group and high glucose control group were cultured in cell culture medium with 5 and 33 mmol/L glucose, respectively. The RNA control group, circRNA-SCAF8 inhibition group, miR-93-5p overexpression group and miR-93-5p inhibition group were added with non-functional siRNA, circRNA-SCAF8 inhibitor, miR-93-5p overexpression molecule and miR-93-5p inhibitor in high glucose environment, respectively. Cell viability and pyroptosis were detected by cell counting kit-8 (CCK-8) assay, flow cytometry and Hoechst 33342/propidium iodide fluorescence double staining. Western blotting and enzyme-linked immunosorbent assay were used to detect the expression of pyroptosis-related factors including apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartic acid specific protease-1 (caspase-1) and Gasdermin D (GSDMD), NOD like receptor protein 3 (NLRP-3), thioredoxin interacting proteins (TXNIP), IL-18 and IL-1β. The expression of circRNA-SCAF8, miR-93-5p and TXNIP was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fluorescence in situ hybridization (FISH) was used to locate circRNA-SCAF8 and miR-93-5p. Dual luciferase assay was used to verify the targeted regulatory relationship between miR-93-5p and upstream and downstream molecules., Results: Compared with the RNA control group, the cell survival rate of circRNA-SCAF8 inhibition group and miR-93-5p overexpression group increased (both P <0.01), the pyroptosis decreased (both P <0.01), and the expressions of pyroptosis-related factors such as TXNIP, NLRP-3, caspase-1, GSDMD, ASC, IL-18 and IL-1β were significantly decreased (all P <0.05). The expression of miR-93-5p was significantly increased after inhibition of circRNA-SCAF8 ( P <0.01), and the expression of circRNA-SCAF8 tended to decrease after overexpression of miR-93-5p, but with no statistical significance ( P >0.05). Dual luciferase assay showed that miR-93-5p downre-gulated circRNA-SCAF8 expression by binding to the 3 ´ UTR region of circRNA-SCAF8, and miR-93-5p downregulated TXNIP expression by binding to the 3 ´ UTR region of TXNIP . FISH showed that circRNA-SCAF8 and miR-93-5p were both located in the cytoplasm and were highly associated in the cells. qRT-PCR showed that the relative expression of TXNIP increased or decreased after overexpression or inhibition of miR-93-5p compared with the RNA control group, respectively (both P <0.05), suggesting that miR-93-5p could regulate TXNIP gene expression., Conclusions: CircRNA-SCAF8/miR-93-5p/TXNIP axis is involved in the regulation of pyroptosis in HUVECs under high glucose.

Recently, several studies have revealed that circular RNAs (circRNAs) play significant roles in various tumors, including lung adenocarcinoma (LUAD). Furthermore, it has been reported that circ&#95;0005962 was upregulated in LUAD cells. Accordingly, this research is designed to investigate the mechanism of circ&#95;0005962 on LUAD development. Circ&#95;0005962, microRNA-3611 (miR-3611), and Cytochrome P450 family 24 subfamily A member 1 (CYP24A1) level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation ability, cell cycle progression, and sphere formation ability were detected using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), Colony formation, flow cytometry, and sphere formation assay. Protein levels of proliferating cell nuclear antigen (PCNA), Ki67, NANOG, CD133, OCT4, and CYP24A1 were determined using Western blot assay. Using bioinformatics software (Starbase3.0 and TargetScan), the binding between miR-3611 and circ&#95;0005962 or CYP24A1 was predicted and proved using RNA Immunoprecipitation (RIP) and RNA pull-down assays. A xenograft tumor model in vivo was used to analyze the biological role of circ&#95;0005962 on LUAD cell growth. Increased circ&#95;0005962 and CYP24A1, and reduced miR-3611 were observed in LUAD tissues and cell lines. Functional assays testified that circ&#95;0005962 depletion might hinder LUAD cell proliferation and sphere formation capability, but induced cell apoptosis in vitro. Molecular mechanism experiments exhibited that circ&#95;0005962 served as a miR-3611 sponge and mediated CYP24A1 content by absorbing miR-3611. Additionally, silencing of circ&#95;0005962 inhibited tumor growth in xenograft modes. Together, circ&#95;0005962 was overexpressed in LUAD, and its deficiency repressed LUAD progression via targeting the miR-3611/ CYP24A1 axis, providing a novel mechanism for understanding the development of LUAD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Wood (secondary xylem) of forests is a material of great economic importance. Wood development is strictly controlled by both the phytohormone auxin and microRNAs (miRNAs). Currently, the regulatory mechanisms underlying wood formation by auxin-associated miRNAs remain unclear., Objective: This report was designed to identify auxin-responsive miRNAs during wood formation., Methods: Morphological observation of wood development in the poplar stems was performed under the treatment of different concentrations (0 mg/L, CK; 5 mg/L, Low; 10 mg/L, High) of indol-3-butyric acid (IBA). Using a small RNA sequencing strategy, the effect of IBA treatment on miRNAs expression was genome-widely analyzed., Results: In this study, we found that wood development of poplar was promoted by low concentration of IBA treatment but inhibited by high concentration of IBA treatment. Stringent bioinformatic analysis led to identification of 118 known and 134 novel miRNAs candidates. Sixty-nine unique developmental-related miRNAs, corresponding to 269 target genes, exhibited specific expression patterns in response to auxin, as was consistent with the influence of auxin application on wood formation. Three novel miRNAs had the most number (≥ 9) of target genes, belonging to SPL, GRF and ARF gene families. The evolutionary relationships and tissue expression patterns of 41 SPL, GRF and ARF genes in poplar were thus analyzed. Of them, four representative members and corresponding miRNAs were confirmed using RT-qPCR., Conclusions: Our results may be helpful for a better understanding of auxin-induced regulation of wood formation in tree species., (© 2023. The Author(s) under exclusive licence to The Genetics Society of Korea.)

Viral immune evasion is crucial to the pathogenesis of hepatitis B virus (HBV) infection. However, the role of HBV in the modulation of innate immune evasion is poorly understood. A liver-specific histone acetyltransferase 1 (Hat1) knockout (KO) mouse model and HAT1 KO cell line were established. Immunohistochemistry staining, Western blot analysis, Southern blot analysis, Northern blot analysis, immunofluorescence assays, enzyme-linked immunosorbent assay, reverse transcription-quantitative polymerase chain reaction, and chromatin immunoprecipitation assays were performed in the livers of mouse models, primary human hepatocytes, HepG2-NTCP, and Huh7 and HepG2 cell lines. HBV-elevated HAT1 increased the expression of miR-181a-5p targeting cyclic GMP-AMP synthase (cGAS) messenger RNA 3' untranslated regions through modulating acetylation of H4K5 and H4K12 in vitro and in vivo, leading to the inability of cGAS-stimulator of interferon genes (STING) pathway and type I interferon (IFN-I) signaling. Additionally, HBV-elevated HAT1 promoted the expression of KPNA2 through modulating acetylation of H4K5 and H4K12 in the system, resulting in nuclear translocation of cGAS, HBx was responsible for the events by HAT1, suggesting that HBV-elevated HAT1 controls the cGAS-STING pathway and IFN-I signaling to modulate viral innate immune evasion. HBV confers innate immune evasion through triggering HAT1/acetylation of H4K5/H4K12/miR-181a-5p or KPNA2/cGAS-STING/IFN-I signaling. Our finding provides new insights into the mechanism by which HBV drives viral innate immune evasion., (© 2023 Wiley Periodicals LLC.)

Background: While adjuvant endocrine therapy (ET) may decrease the mortality rate of estrogen receptor-positive (ER+) breast cancer (BC), the likelihood of relapse and metastasis due to ET resistance remains high. Cuproptosis is a recently discovered regulated cell death (RCD), whose role in tumors has yet to be elucidated. Thus, there is a need to study its specific regulatory mechanism in resistance to ET in BC, to identify novel therapeutic targets., Methods: The prognostic cuproptosis-related genes (CRGs) in ER+ BC were filtered by undergoing Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses in TCGA-BRCA, and a CRGs risk signature was constructed using the correlation coefficient. Immune infiltration analysis, immune function analysis, tumor microenvironment (TME) analysis, immune checkpoint analysis, immunotherapy response analysis, drug sensitivity analysis, and pathway activation analysis were carried out among the high- and low-risk groups in turn. The central CRG of cuproptosis in ER+ BC resistance to ET was acquired through the intersection of protein interaction network (PPI) analysis, genes differentially expressed (DEGs) between human BC cells LCC9 and MCF-7 (GSE159968), and CRGs with prognostic significance in TCGA-BRCA ER+ BC. The miRNAs upstream of the core CRGs were predicted based on the intersection of 4 databases, miRDB, RNA22, miRWalk, and RNAlnter. Candidate miRNAs consisted of the intersection of predicted miRNAs and miRNAs differentially expressed in the LCC9 and MCF-7 cell lines (GSE159979). Candidate lncRNAs were the intersection of the differential lncRNAs from the LCC9 and MCF-7 cell lines and the survival-related lncRNAs obtained from a univariate Cox regression analysis. Pearson's correlation analysis was performed between mRNA-miRNA, miRNA-lncRNA, and mRNA-lncRNA expression separately., Results: We constructed A risk signature of 4-CRGs to predict the prognosis of ER+ BC in TCGA-BRCA, a risk score = DLD*0.378 + DBT*0.201 + DLAT*0.380 + ATP7A*0.447 was used as the definition of the formula. There were significant differences between the high- and low-risk groups based on the risk score of 4-CRGs in aspects of immune infiltration, immune function, expression levels of immune checkpoint genes, and signaling pathways. DLD was determined to be the central CRG of cuproptosis in ER+ BC resistance to ET through the intersection of the PPI network analysis, DEGs between LCC9 and MCF-7 and 4-CRGs. Two miRNAs hsa-miR-370-3p and hsa-miR-432-5p were found taking DLD mRNA as a target, and the lncRNA C6orf99 has been hypothesized to be a competitive endogenous RNA that regulates DLD mRNA expression by sponging off hsa-miR-370-3p and hsa-miR-432-5p., Conclusion: This study built a prognostic model based on genes related to cuproptosis in ER+ BC. We considered DLD to be the core gene associated with resistance to ET in ER+ BC via copper metabolism. The search for promising therapeutic targets led to the establishment of a cuproptosis-related ceRNA network C6orf99/hsa-miR-370-3p and hsa-miR-432-5p/DLD., (© 2023. The Author(s).)

Naked cuticle homolog 1 (NKD1), which is expressed at low levels in many tumors, is considered an inhibitor of the Wnt/β-catenin pathway, but it is highly expressed in colon cancer and can promote colon cancer cell proliferation. miRNAs are involved in the occurrence and progression of many tumors. However, miRNAs that can regulate NKD1 and the mechanisms by which NKD1 regulates tumor progression remain ambiguous. This research aims to reveal the potential regulatory network of NKD1 in colon cancer. miRNA data downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were analyzed by bioinformatics to screen for potential miRNAs targeting NKD1. Let-7b-5p was found to inhibit proliferation, migration, and invasion of colon cancer cells targeting NKD1. Further studies suggested that let-7b-5p can modulate Wnt signaling activity, and the nuclear accumulation of β-catenin was significantly restrained by let-7b-5p through targeting NKD1. Moreover, NKD1 could prohibit the expression of the APC protein. Further studies manifested that NKD1 bound to APC and promoted the ubiquitination degradation of APC through restraining the expression of the deubiquitinating enzyme USP15 and blocking the combination between USP15 and APC. Functionally, NKD1 enhanced the proliferation and migration of colon cancer cells by inhibiting APC expression. This research revealed a novel mechanism by which the let-7b-5p-NKD1-APC-β-catenin signaling pathway inhibited colon cancer cell progression., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Exosomes derived from mesenchymal stem cells have shown therapeutic effects for colitis. As a more clinically accessible resource, the therapeutic potential of exosomes from adipose-derived stem cells (ASCs) has not been fully elucidated, and whether hypoxia precondition could improve the therapeutic effect of ASC-derived exosomes in colitis remains elusive., Methods: In this study, exosomes were derived from ASCs under normoxia (NExos) and hypoxia (HExos) and were identified by detecting their morphology, size distribution, and exosome surface markers. The concentration of inflammation-related cytokines was detected by ELISA, and macrophage phenotype-related genes were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blot, and immunofluorescence. A miRNA microarray sequencing analysis was conducted to confirm the differentially expressed miRNAs. Dextran sulfate sodium-induced colitis was employed as an in vivo assay., Results: Administration of NExos alleviated inflammation by modulating the balance of macrophages both in cellular assays and in vivo experiments, and HExos showed higher therapeutic efficiency than NExos. The miR-216a-5p in HExos was significantly enriched and promoted macrophage M2 polarization through transfer to macrophages by exosomes. The miR-216a-5p was confirmed to target the 3'-UTR of HMGB1. Mechanistically, hypoxia-induced ASCs release miR-216a-5p in an exosomal way that induced macrophage M2 polarization by regulating the HMGB1/TLR4/NF-κB signaling pathway., Conclusions: Exosomal miR-216a-5p released from hypoxia-prime ASCs showed higher therapeutic efficiency than NExos in experimental colitis by promoting the M2 macrophage phenotype, which indicated that hypoxia prime may represent a promising approach to optimizing the function of ASC-derived exosomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: To explore the effect and its specific mechanism of miR-155-5p on M1 polarization of Kupffer cells (KCs) and immune response in liver transplantation (LT) through KDM5D., Methods: Primary KCs were isolated from Wistar rats and identified by cell culture, ink-swallowing test and flow cytometry. The cells identified as KCs were induced into LT acute rejection (AR) model cells by LPS/IFN-γ, flow cytometry was used for cell sorting and apoptosis detection. Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the levels of inflammatory factors, macrophages and liver function markers. RT-qPCR detected the expression of miR-155-5p and KDM5D mRNA. The protein expression of KDM5D was detected by Western blot. Dual luciferase reporter gene experiment verified the targeting relationship between miR-155-5p and KDM5D., Results: The separated KCs adhered after being cultured for 24 h, had pseudopodia and phagocytosis, and the proportion of F4/80 positive cells was more than 90%. The expression of miR-155-5p was increased in LPS/IFN-γ-induced KCs. And knockdown of miR-155-5p inhibited H3K4me3 and H3K27me3 of TNF-α promoter, M1 polarization of KCs and the immune response of AR model cells by upregulating KDM5D. In animal experiments, knockdown of miR-155-5p was found to inhibit liver damage and immune response in rats with allogeneic orthotopic LT., Conclusion: These results confirmed that miR-155-5p inhibited M1 polarization of KCs induced by LPS/IFN-γ, thereby alleviating AR and liver function impairment after LT by upregulating KDM5D., Competing Interests: Conflict of interest The authors declare that there is no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Heart failure (HF) is often the inevitable manifestation of myocardial ischemia. Hypoxia can induce cardiomyocytes to express many microRNAs (miRNAs), which are highly expressed in exosomes. In addition, miR-22-3p is a marker in heart failure. Therefore, miR-22-3p was taken as the research object to explore its role and mechanism in HF. HF differentially expressed miRNAs were screened by bioinformatic analysis. The HF rats model was constructed and identified by detecting serum brain natriuretic peptide (BNP) and ultrasound analysis [left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS)]. The extracted exosomes were identified by transmission electron microscopy, and Western blot was used to detect the expressions of Tsg101 and CD63. Quantitative real-time polymerase chain reaction detected miR-22-3p expression in serum, exosomes, and serum without exosomes, while the cardiomyocytes cytotoxicity was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and PKH26 staining. After overexpressing/silencing miR-22-3p in cells, cell viability, apoptosis, and apoptosis-associated markers were detected. Bioinformatic analysis screened the target gene of miR-22-3p, which was verified by dual-luciferase assay. Regulation of miR-22-3p on FURIN was measured by rescue tests. In vivo experiments were verified the above results. MiR-22-3p was identified as the research object. BNP was increased in the model group, while LVEF and LVFS were decreased. MiR-22-3p was overexpressed in HF-treated serum and exosomes. Normal exosomes did not affect cardiomyocyte function, while high concentrations of HF-treated exosomes were cytotoxic. By regulating apoptosis-related genes, overexpressed miR-22-3p inhibited cell activity and promoted cell apoptosis. Silenced miR-22-3p with opposite effects counteracted effects of HF-treated exosomes. FURIN, target gene of miR-22-3p, was negatively regulated by miR-22-3p, while overexpressed FURIN promoted cell activity and inhibited apoptosis. In vivo research was consistent with the results of cell experiments. By regulating FURIN, miR-22-3p in exosomes increases the risk of HF damage., (© 2022 John Wiley & Sons Ltd.)

Ovarian cancer is one of the most common gynecologic malignancies with a highly immunosuppressive tumor microenvironment (TME) and poor prognosis. Circular RNA (circRNA) is a type of noncoding RNA with high stability, which has been shown to play an important role in biological processes and TME reprogramming in a variety of tumors. The biological function of a novel circRNA, circATP2B4, in epithelial ovarian cancer (EOC) was detected and evaluated. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of extracellular vesicles (EV)-packaged circATP2B4. Macrophage uptake of circATP2B4 was determined by EVs tracing. Dual luciferase reporter, FISH, Western blotting, and flow cytometry assays were used to investigate the interactions between circATP2B4 and miR-532-3p as well as sterol regulatory element-binding factor 1 (SREBF1) expression in macrophages. CircATP2B4 was upregulated in EOC tissues and positively correlated with ovarian cancer progression. Functionally, circATP2B4 promoted carcinogenic progression and metastasis of EOC both in vitro and in vivo. Mechanistically, EV-packaged circATP2B4 in EOC could be transmitted to infiltrated macrophages and acted as competing endogenous RNA of miR-532-3p to relieve the repressive effect of miR-532-3p on its target SREBF1. Furthermore, circATP2B4 induced macrophage M2 polarization by regulating the miR-532-3p/SREBF1/PI3Kα/AKT axis, thereby leading to immunosuppression and ovarian cancer metastasis. Collectively, these data indicate that circATP2B4-containing EVs generated by EOC cells promoted M2 macrophages polarization and malignant behaviors of EOC cells. Thus, targeting EVs-packaged circATP2B4 may provide a potential diagnosis and treatment strategy for ovarian cancer., (©2022 The Authors; Published by the American Association for Cancer Research.)

Background: Glucocorticoids (GCs) are commonly used to treat autoimmune diseases and malignancies in children and adolescents. Growth retardation is a common adverse effect of GC treatment in pediatric patients. Accumulating evidence indicates that non-coding RNAs (ncRNAs) are involved in the pathogenesis of glucocorticoid-induced growth retardation (GIGR), but the roles of specific ncRNAs in growth remain largely unknown., Methods: In this study, 2-week-old male Sprague-Dawley rats had been treated with 2 mg/kg/d of dexamethasone for 7 or 14 days, after which the growth plate tissues were collected for high-throughput RNA sequencing to identify differentially expressed mRNAs, lncRNAs, circRNAs, and miRNAs in GIGR rats., Results: Transcriptomic analysis identified 1,718 mRNAs, 896 lncRNAs, 60 circRNAs, and 72 miRNAs with different expression levels in the 7d group. In the 14d group, 1,515 mRNAs, 880 lncRNAs, 46 circRNAs, and 55 miRNAs with differential expression were identified. Four mRNAs and four miRNAs that may be closely associated with the development of GIGR were further validated by real-time quantitative fluorescence PCR. Function enrichment analysis indicated that the PI3K-Akt signaling pathway, NF-kappa B signaling pathway, and TGF- β signaling pathway participated in the development of the GIGR. Moreover, the constructed ceRNA networks suggested that several miRNAs (including miR-140-3p and miR-127-3p) might play an important role in the pathogenesis of GIGR., Conclusions: These results provide new insights and important clues for exploring the molecular mechanisms underlying GIGR., Competing Interests: The authors declare there are no competing interests., (©2023 Yin et al.)

Background: Ovarian cancer remains a leading cause of mortality in women. It is known that long non-coding RNA (lncRNA) controls various biological processes and pathogenesis of many diseases, including cancers. This study aimed to determine whether LINC00936 and microRNA-221-3p (miR-221-3p) influence the laminin alpha 3 chain gene (LAMA3) in the development of ovarian cancer., Methods: The expressions of LINC00936, miR-221-3p, and LAMA3 in ovarian cancer and adjacent tissues were assessed. Furthermore, ovarian cancer cells were transfected with vectors with overexpressed LINC00936, miR-221-3p mimic, miR-221-3p inhibitor, and si-LAMA3 to elucidate their functions in ovarian cancer cell proliferation, migration, invasion, angiogenesis, and tumorigenesis. The binding relationship between LINC00936 and miR-221-3p and the relationship between miR-221-3p and LAMA3 were verified to explore the mechanism of action of LINC00936 in ovarian cancer. LINC00936 binds to miR-221-3p as a ceRNA and regulates the expression of LAMA3., Results: LINC00936 and LAMA3 were poorly expressed, while miR-221-3p was highly expressed in ovarian cancer tissues. Over-expression of LINC00936 contributed to decreasing miR- 221-3p expression and increasing LAMA3 expression. LINC00936 overexpression or miR-221- 3p silencing downregulated the levels of PCNA, MMP-2, MMP-9, and VEGF and decreased cell proliferation, migration, invasion, angiogenesis, and ovarian cancer tumorigenesis., Conclusion: Collectively, overexpression of LINC00936 suppressed the development of ovarian cancer by competitively binding to miR-221-3p and controlling LAMA3 expression. These results could serve as a novel theoretical base for the treatment of ovarian cancer., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Patients with osteoporosis (OP) have a high risk of bone fracture. Abnormal bone mesenchymal stem cell (BMSC) differentiation is an essential process of OP development. In recent years, photobiomodulation has been shown to effectively promote BMSC proliferation. However, the mechanism by which photobiomodulation promotes BMSC proliferation is unclear. Long noncoding RNAs (lncRNAs) are essential mediators in multiple biological processes. The lncRNA maternally expressed gene 3 (MEG3) is a novel lncRNA gene and is related to cell proliferation. Studies have indicated that MEG3 serves as a promotor in BMSC proliferation. Objective: To investigate the effects and mechanisms of 800 nm light-emitting diode (LED) photobiomodulation in BMSC proliferation. Materials and methods: The BMSCs collected from mouse tibias and femurs were irradiated by 800 nm LED for 180 sec. CCK-8 assay was used to detect the cell viability. A dual-luciferase reporter assay was used to determine IncRNA MEG3 acted as a miR-217-5p sponge. We used reverse transcription-polymerase chain reaction (RT-PCR) and western blot to detect the mRNA and protein levels of MEG3, miR-217-5p, Notch2, Hes1, Hey2. Results: In the present study, we revealed that photobiomodulation (800 nm LED) could increase the mRNA level of MEG3, and protein levels of Notch2, Hes1, and Hey2. Moreover, we also identified that upregulated MEG3 could act as a miR-217-5p sponge to activate the Notch signaling pathway. Conclusions: The current study revealed the MEG3-related mechanism of photobiomodulation treatment in OP and identified potential gene therapies for OP.

Ischemic stroke is one of major causes of disability. In the pathological process of ischemic stroke, the up-regulation of Ras homolog gene family, member A (RhoA) and its downstream effector, Ras homolog gene family (Rho)-associated coiled coil-containing kinase (ROCK), contribute to the neuroinflammation, blood-brain barrier (BBB) dysfunction, neuronal apoptosis, axon growth inhibition and astrogliosis. Accumulating evidences have revealed that hydrogen sulphide (H 2 S) could reduce brain injury in animal model of ischemic stroke via inhibiting the RhoA/ROCK pathway. Recently, noncoding RNAs (ncRNAs) such as circular RNAs (circRNAs), long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have attracted much attention because of their essential role in adjusting gene expression both in physiological and pathological conditions. Numerous studies have uncovered the role of RhoA/ROCK pathway and ncRNAs in ischemic stroke. In this review, we focused on the role of H 2 S, RhoA/ROCK pathway and ncRNAs in ischemic stroke and aimed to reveal new strategies for preventing and treating this devastating disease., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the expression and clinical significance of let-7a and tumor necrosis factor-alpha (TNF-α) in placental tissue of patients with severe preeclampsia (SPE)., Methods: From January 2018 to October 2019, 64 cases of puerperal delivery at the First People's Hospital of Lianyungang City, 44 cases of SPE (SPE group), and 20 cases of healthy pregnant women (NC group) were selected. QRT-PCR and Western-blot were used to detect the expression levels of let-7a, TNF-αmRNA, and protein in the two groups of placental tissues. The correlation and the clinical significance of the two were statistically analyzed., Results: The relative expression of let-7a in the SPE group was significantly lower than that in the control group (0.06 ± 0.02 versus 0.25 ± 0.04, p  < .05); the expression of TNF-αmRNA in the SPE group was significantly higher than that in the control group (0.48 ± 0.04 versus 0.17 ± 0.03, p  < .05); TNF-α protein expression was significantly increased in the SPE group (1.09 ± 0.12 versus 0.56 ± 0.03, p  < .05); let-7a and TNF-α were significantly negatively correlated ( r = -0.41, p  < .05); the blood pressure and birth weight of the pregnant women in the SPE group and the control group were significantly different [systolic blood pressure (164.27 ± 4.62) mmHg versus (125.01 ± 2.23)] mmHg, diastolic blood pressure (109.24 ± 2.97) mmHg versus (75.94 ± 2.74) mmHg, neonatal birth weight (2507.02 ± 161.46) g versus (3592.12 ± 153.05) g, p  < .05]; the expression of TNF-α in placental tissue of SPE group was significantly positively correlated with systolic and diastolic blood pressure ( r  = 0.93 and 0.89, p  < .05)., Conclusion: let-7a may participate in the occurrence and development of SPE by negatively regulating the expression of TNF-α.

Objective: To explore the effect and mechanism of the miR-339-3p/KAT6A/TRIM24 axis in nasopharyngeal carcinoma (NPC) cell growth and epithelial-mesenchymal transition (EMT) progression., Methods: CNE2 and 5-8F NPC cell lines were transfected with miR-339-3p-mimic or sh-KAT6A alone or co-transfected with miR-339-3p-mimic and oe-KAT6A. The expression levels of miR-339-3p, KAT6A, TRIM24, and EMT-related proteins were assessed, in addition to cell biological behaviors. Then, the relationship between miR-339-3p and KAT6A was predicted and validated. The correlations between miR-339-3p and KAT6A or between KAT6A and TRIM24 were analyzed by Pearson coefficient and the enrichment of H3K23ac in TRIM24 promoter region was measured by chromatin immunoprecipitation., Results: miR-339-3p was downregulated, but KAT6A and TRIM24 were highly expressed in NPC cells and tissues. Upregulated miR-339-3p or downregulated KAT6A could inhibit the growth and EMT of NPC cells. Further experiments showed that miR-339-3p regulated NPC cell growth and EMT by mediating KAT6A in a targeted fashion. KAT6A was positively correlated with TRIM24, and the enrichment of H3K23ac was much higher in NPC tissues. miR-339-3p suppressed the growth and EMT of NPC cells by the KAT6A/TRIM24 axis. In a xenograft study, miR-339-3p overexpression inhibited NPC tumor growth in vivo., Conclusion: Conclusively, miR-339-3p inhibited the growth and EMT of NPC cells via the KAT6A/TRIM24 axis., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

The manuscript is being retracted due to non-original and duplicated content in the figure images, which raise concerns regarding the credibility of the study. Reference: Wusheng Lu, Jinhuang Lin, Dequan Zheng, Chunyong Hong, Laishun Ke, Xinyu Wu, Peineng Chen. Overexpression of MicroRNA-133a Inhibits Apoptosis and Autophagy in a Cell Model of Parkinson's Disease by Downregulating Ras-Related C3 Botulinum Toxin Substrate 1 (RAC1). Med Sci Monit, 2020; 26: e922032. DOI: 10.12659/MSM.922032.

Abdominal aortic aneurysm (AAA) refers to local abnormal expansion of the abdominal aorta and mostly occurs in elderly men. MicroRNA (miRNA) is single-stranded RNA consisting of 18-25 nucleotides. It plays a key role in posttranscriptional gene expression and in the regulation of human functions and disease development. miRNA exerts its function mainly through the binding of complementary base pairs to the 3' regulatory region of mRNA transcripts. Therefore, miRNA-related single-nucleotide polymorphisms (miRSNPs) can affect miRNA expression and processing kinetics. miRSNPs can be classified based on their location: miRSNPs within miRNA-producing genes and miRSNPs within miRNA target genes. Increasing evidence indicates that miRSNPs play an important role in the pathogenic kinetics of cardiovascular diseases. The aim of this study was to identify potential miRNAs and integrate them into a miRSNP-based disease-related pathway network, the results of which are of great significance to the interpretation of the potential mechanisms and functions of miRSNPs in the pathogenesis of diseases., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Shenrong Liu et al.)

Background: Osteoarthritis (OA) is a severe disabling condition that causes major health problems. The roles of long non-coding RNAs (lncRNAs) in regulating OA progression have been increasingly researched. Based on previously published microarray analysis, LINC00707 is upregulated in OA. This research was done to uncover the function of LINC00707 in IL-1β-induced chondrocyte injury and its possible mechanisms., Methods: LINC00707, miR-330-5p, and follicle-stimulating hormone receptor (FSHR) expression in OA cartilage tissues were assessed by RT-qPCR. Primary chondrocytes were isolated from OA tissues and treated with IL-1β to establish an in vitro OA model. Under the indicated treatment, chondrocyte apoptosis, senescence, ECM degradation, and inflammation were determined using flow cytometry, TUNEL, SA-β-Gal staining, and ELISA experiments, respectively. Interactions between gene were evaluated using Ago2 RIP and luciferase reporter assays., Results: LINC00707 and FSHR were elevated, and miR-330-5p was reduced in cartilage tissues of OA patients and in IL-1β-treated primary chondrocytes. Silencing LINC00707 hampered chondrocytes apoptosis, senescence, ECM degradation, and inflammation. LINC00707 acted as a ceRNA to regulate FSHR through controlling miR-330-5p availability. Additionally, both miR-330-5p depletion and FSHR overexpression diminished the effects of silencing LINC00707 in OA progression., Conclusions: Silencing LINC00707 mitigates chondrocyte injury in osteoarthritis via sponging miR-330-5p and inhibiting FSHR.

Lung cancer is devastating cancer that ranks as the leading cause of cancer-related death. Long noncoding RNA (lncRNA) opioid growth factor receptor pseudogene 1 (OGFRP1) was recognized as an oncogene in many cancers. However, the molecular mechanism of OGFRP1 in lung cancer is still poorly understood. The expression of target RNAs and genes was detected by quantitative real-time PCR and western blot. The interaction between miR-299-3p and OGFRP1 or solute carrier family 38 member 1 (SLC38A1) was predicted by StarbaseV3.0 and verified by dual-luciferase reporter assay and Pearson's correlation coefficient. Besides, a transplantation model of human lung cancer in nude mice was established to evaluate the role of OGFRP1 in lung cancer. OGFRP1 and SLC38A1 were overexpressed, whereas miR-299-3p was lowly expressed in lung cancer tumors and cells. OGFRP1 knockdown suppressed cell proliferation and facilitated ferroptosis by promoting lipid peroxidation and iron accumulation in lung cancer. Besides, Furthermore, miR-299-3p inhibitor or SLC38A1 overexpression attenuated OGFRP1 depletion-induced suppression on cell proliferation and ferroptosis in lung cancer. Animal experiments indicated that OGFRP1 deficiency restrained tumor growth in vivo by regulating the miR-299-3p/SLC38A1 axis. OGFRP1 regulated cell proliferation and ferroptosis in lung cancer by inhibiting miR-299-3p to enhance SLC38A1 expression, providing a novel therapeutic strategy for lung cancer., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Lung cancer is a highly aggressive and metastatic disease responsible for approximately 25% of all cancer-related deaths in the United States. Using high-throughput in vitro and in vivo screens, we have previously established Impad1 as a driver of lung cancer invasion and metastasis. Here we elucidate that Impad1 is a direct target of the epithelial microRNAs (miRNAs) miR-200 and miR∼96 and is de-repressed during epithelial-to-mesenchymal transition (EMT); thus, we establish a mode of regulation of the protein. Impad1 modulates Golgi apparatus morphology and vesicular trafficking through its interaction with a trafficking protein, Syt11. These changes in Golgi apparatus dynamics alter the extracellular matrix and the tumor microenvironment (TME) to promote invasion and metastasis. Inhibiting Impad1 or Syt11 disrupts the cancer cell secretome, regulates the TME, and reverses the invasive or metastatic phenotype. This work identifies Impad1 as a regulator of EMT and secretome-mediated changes during lung cancer progression., Competing Interests: Declaration of interests D.L.G. declares advisory board work for AstraZeneca, Eli Lilly, Menarini Richerche, 4D Pharma, and Sanofi. D.L.G. has received research grant funding from AstraZeneca, Janssen, Astellas, Ribon Therapeutics, NGM Biotherapeutics, and Takeda., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)