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Background: Epithelial-mesenchymal transition (EMT) plays a crucial role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, the involvement of small extracellular vesicles (sEVs) in EMT and their contributions to CRSwNP has not been extensively investigated., Methods: SEVs were isolated from nasal mucosa through ultracentrifugation. MicroRNA sequencing and reverse-transcription quantitative polymerase chain reaction were employed to analyze the differential expression of microRNAs carried by sEVs. Human nasal epithelial cells (hNECs) were used to assess the EMT-inducing effect of sEVs/microRNAs. EMT-associated markers were detected by western blotting and immunofluorescence. Dual-luciferase reporter assay was performed to determine the target gene of miR-375-3p. MicroRNA mimic, lentiviral, and plasmid transduction were used for functional experiments., Results: In line with the greater EMT status in eosinophilic CRSwNP (ENP), sEVs derived from ENP (ENP-sEVs) could induce EMT in hNECs. MiR-375-3p was elevated in ENP-sEVs compared to that in control and nonENP. MiR-375-3p carried by ENP-sEVs facilitated EMT by directly targeting KH domain containing RNA binding (QKI) at seed sequences of 913-919, 1025-1033, and 2438-2444 in 3’-untranslated region. Inhibition of QKI by miR-375-3p overexpression promoted EMT, which could be reversed by restoration of QKI. Furthermore, the abundance of miR-375-3p in sEVs was closely correlated with the clinical symptom score and disease severity., Conclusions: MiR-375-3p-enriched sEVs facilitated EMT by suppressing QKI in hNECs. The association of miR-375-3p with disease severity underscores its potential as both a diagnostic marker and a therapeutic target for the innovative management of CRSwNP.

Chronic wound rescue is critical for diabetic patients but is challenging to achieve with a specific and long-term strategy. The prolonged bacterial inflammation is particularly prevalent in hyperglycemia-induced wounds, usually leading to severe tissue damage. Such a trend could further suffer from an environmental suitability provided by macrophages for persisting Staphylococcus aureus ( S. aureus ) and even deteriorate by their mutual reinforcement. However, the strategy of both suppressing bacteria growth and immunoreprogramming the inflammatory type of macrophages to break their vicious harm to wound healing is still lacking. Here, a self-adapting biomass carboxymethyl chitosan (CMC) hydrogel comprising immunomodulatory nanoparticles is reported to achieve Gram-negative/Gram-positive bacteria elimination and anti-inflammatory cytokines induction to ameliorate the cutaneous microenvironment. Mechanistically, antibacterial peptides and CMCs synergistically result in a long-term inhibition against methicillin-resistant S. aureus (MRSA) over a period of 7 days, and miR-301a reprograms the M2 macrophage via the PTEN/PI3Kγ/mTOR signaling pathway, consequently mitigating inflammation and promoting angiogenesis for diabetic wound healing in rats. In this vein, immunoregulatory hydrogel is a promising all-biomass dressing ensuring biocompatibility, providing a perspective to regenerate cutaneous damaged tissue, and repairing chronic wounds on skin.

Metformin, a widely used anti-diabetic drug, has demonstrated its efficacy in addressing various inflammatory conditions. tRNA-derived small RNA (tsRNA), a novel type of small non-coding RNA, exhibits diverse regulatory functions and holds promise as both a diagnostic biomarker and a therapeutic target for various diseases. The purpose of this study is to investigate whether the abundance of tsRNAs changed in LPS versus LPS + metformin-treated cells, utilizing microarray technology. Firstly, we established an in vitro lipopolysaccharide (LPS)-induced inflammation model using RAW264.7 macrophages and assessed the protective effects of metformin against inflammatory damage. Subsequently, we extracted total RNA from both LPS-treated and metformin + LPS-treated cell samples for microarray analysis to identify differentially abundant tsRNAs (DA-tsRNAs). Furthermore, we conducted bioinformatics analysis to predict target genes for validated DA-tsRNAs and explore the biological functions and signaling pathways associated with DA-tsRNAs. Notably, metformin was found to inhibit the inflammatory response in RAW264.7 macrophages. The microarray results revealed a total of 247 DA-tsRNAs, with 58 upregulated and 189 downregulated tsRNAs in the Met + LPS group compared to the LPS group. The tsRNA-mRNA network was visualized, shedding light on potential interactions. The results of bioinformatics analysis suggested that these potential targets of specific tsRNAs were mainly related to inflammation and immunity. Our study provides compelling evidence that metformin exerts anti-inflammatory effects and modulates the abundance of tsRNAs in LPS-treated RAW264.7 macrophages. These findings establish a valuable foundation for using tsRNAs as potential biomarkers for metformin in the treatment of inflammatory conditions., 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.)

Abdominal aortic aneurysm (AAA) is a cardiovascular disease that seriously threatens human health and brings huge economic burden. At present, its pathogenesis remains unclear and its treatment is limited to surgical treatment. With the deepening and analysis of studies on the mechanism of ferroptosis, a new idea has been provided for the clinical management of AAA patients, including diagnosis, treatment and prevention. Therefore, this paper aims to construct a competitive endogenous RNA (ceRNA) regulatory axis based on ferroptosis to preliminarily explore the pathogenesis and potential therapeutic targets of AAA. We obtained upregulated and downregulated ferroptosis-related DEGs (FRGs) from GSE144431 dataset and 60 known ferroptosis-related genes. Pearson correlation analysis was used to find aldoketone reductase 1C (AKR1C1) in AAA samples. Enrichment analysis of these genes was performed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Correlation test between immune cells and AKR1C1 was investigated through single-sample gene set enrichment analysis (ssGSEA). The AKR1C1-miRNA pairs were predicted by the TargetScan database and miRWalk database. Circular RNA (CircRNA)-miRNA pairs were selected by the CircInteractome database. Overlapping miRNA between circRNA-miRNA and AKR1C1-miRNA pairs was visualized by Venn diagram. Finally, the circRNA-miRNA-mRNA axis was constructed by searching for upstream circRNA and downstream mRNA of overlapping miRNA. Only one downregulated AKR1C1 gene was found in GSE144431 and 60 ferroptosis-related genes. Functional Enrichment and Pathway Analysis of AKR1C1-related genes were further explored, and it was observed that they were mainly enriched in "response to oxidative stress," "glutathione biosynthetic process" and "nonribosomal peptide biosynthetic process," "Ferroptosis," "Glutathione metabolism" and "Chemical carcinogenesis-reactive oxygen species." They were also found to be significantly associated with most immune cells, including Activated Dendritic cells, CD56dim Natural killer cells, Gamma Delta T cells, Immature B cells, Plasmacytoid dendritic cell, Type 2 T helper cell, Activated CD4 T cell and Type 1 T helper cell. Has_circ_0005073-miRNA-543 and AKR1C1-miRNA-543 were identified by Online Database analysis. Therefore, we have established the has_circ_0005073/miRNA-543/AKR1C1 axis in AAA. We found AKR1C1 was differentially expressed between normal and AAA groups. Based on AKR1C1, we constructed the has_circ_0005073/miRNA-543/AKR1C1 axis to analyze AAA., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored., Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression., Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy., Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Lu et al.)

Colorectal cancer (CRC) is a type of intestinal cancer that causes more than 600,000 deaths every year. Overcoming the problems of metastasis requires detailed studies to reveal the potential molecular mechanisms. This study aims to reveal the molecular mechanism of CRC metastasis involving non-coding RNA regulation. The expression profile of FTH1P3 was analyzed based on the data of TCGA-COAD patient cohorts. Q-PCR analysis was performed to validate the expression of FTH1P3 in colorectal cancer cells. JASPR was used to screen transcription factors of FTH1P3. q-ChIP analysis was used to validate the target between FTH1P3 and transcription factor. Scratch assay and transwell assay were used to evaluate the migration and invasion ability of colorectal cancer cells. FTH1P3 is highly expressed in CRC patient cohort. FTH1P3 induced migration and invasion of SW480 cell through regulating epithelial-mesenchymal transition (EMT). In addition, FTH1P3 is a direct target of SNAI2. SNAI2 promotes the expression of FTH1P3. Both FTH1P3 and SNAI2 were directly targeted and repressed by miR-218-5p. Interestingly, ectopic FTH1P3 caused a decreased miR-218-5p level and an elevated nucleic SNAI2 protein expression level. Of note, only ectopic SNAI2 protein resulted in a repressed miR-218-5p and an increased FTH1P3, whereas SNAI2 3'UTR failed to affect the expression of miR-218-5p and FTH1P3. SNAI2 transcriptionally activates FTH1P3 expression. Both SNAI2 and FTH1P3 are targets of miR-218-5p. SNAI2/FTH1P3/miR-218-5p form a positive feedback loop in the regulation of CRC metastasis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The most significant and sensitive antigen protein that causes diarrhea in weaned pigs is soybean 7S globulin. Therefore, identifying the primary target for minimizing intestinal damage brought on by soybean 7S globulin is crucial. MicroRNA (miRNA) is closely related to intestinal epithelium's homeostasis and integrity. However, the change of miRNAs' expression and the function of miRNAs in Soybean 7S globulin injured-IPEC-J2 cells are still unclear. In this study, the miRNAs' expression profile in soybean 7S globulin-treated IPEC-J2 cells was investigated. Fifteen miRNAs were expressed differently. The differentially expressed miRNA target genes are mainly concentrated in signal release, cell connectivity, transcriptional inhibition, and Hedgehog signaling pathway. Notably, we noticed that the most significantly decreased miRNA was ssc-miR-221-5p after soybean 7S globulin treatment. Therefore, we conducted a preliminary study on the mechanisms of ssc-miR-221-5p in soybean 7S globulin-injured IPEC-J2 cells. Our research indicated that ssc-miR-221-5p may inhibit ROS production to alleviate soybean 7S globulin-induced apoptosis and inflammation in IPEC-J2 cells, thus protecting the cellular mechanical barrier, increasing cell proliferation, and improving cell viability. This study provides a theoretical basis for the prevention and control of diarrhea of weaned piglets.

Abstract: Myocardial ischemia-reperfusion injury (MIRI) is a vital risk factor for cardiovascular diseases. Some circular RNAs have been identified as modulators of MIRI. However, the effects of circ-mitochondrial amidoxime reducing component 2 (circ-MARC2) in MIRI are unclear. Our results showed that circ-MARC2 was overexpressed in hypoxia/reoxygenation (H/R)-treated AC16 cells. Circ-MARC2 silencing reversed the inhibitory effect of H/R treatment on cell proliferation and promoting effects on lactate dehydrogenase activity, creatine kinase activity, and cell apoptosis in AC16 cells. Moreover, circ-MARC2 served as the sponge for miR-335-5p and ameliorated H/R-induced AC16 cell damage by decoying miR-335-5p. In addition, transient receptor potential cation channel subfamily M member 7 (TRPM7) was identified as the target gene of miR-335-5p. Overexpression of miR-335-5p relieved H/R-induced AC16 cell damage, whereas TRPM7 elevation abolished the effect. Circ-MARC2 knockdown was able to relieve H/R-induced AC16 cell injury through miR-335-5p/TRPM7 axis., Competing Interests: Disclosure of interest: The authors declare that they have no conflicts of interest., (Copyright © 2023 by the Shock Society.)

The management of skin wound healing is still a challenge. MicroRNA-21 (miR-21) has been reported to play important roles in wound repair; however, the underlying mechanism needs to be further clarified. The present study aimed to study the direct role of miR-21 in skin wound healing in miR-21 KO mice and to investigate the role of miR-21 in controlling the migration and proliferation of primary human skin cells and its underlying mechanism(s). miR-21 KO and wild-type (WT) mice were used for in vivo wound healing assays, while mouse and human primary skin cells were used for in vitro assays. miR-21 inhibitors or mimics or negative control small RNAs were transfected to either inhibit or enhance miR-21 expression in the human primary dermal fibroblasts or epidermal cells. RNA sequencing analysis was performed to identify the potential molecular pathways involved. We found that the loss of miR-21 resulted in slower wound healing in miR-21 KO mouse skin and especially delayed the healing of dermal tissue. In vitro assays demonstrated that the reduced expression of miR-21 caused by its inhibitor inhibited the migration of human primary dermal fibroblasts, which could be enhanced by increased miR-21 expression caused by miR-21 mimics. RNA-sequence analysis revealed that the inhibition of miR-21 expression downregulated the inflammatory response pathways associated with the decreased expression of inflammatory cytokines, and the addition of IL-1β into the culture medium enhanced the migration and proliferation of dermal fibroblasts in vitro. In conclusion, miR-21 in dermal fibroblasts can promote the migration and growth of epidermal and dermal cells to enhance skin wound healing through controlling the expression of inflammatory cytokines., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA-miRNA-lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW's regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA's progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA., (© 2024. The Author(s).)

Hepatitis B virus (HBV) infection is associated with male infertility. The mechanism includes an increase in chromosomal instability in sperm, which has an adverse effect on sperm viability and function. Sertoli cells (SCs) are vital in spermatogenesis because they use glycolysis to provide energy to germ cells and themselves. HBV infection impairs sperm function. However, whether HBV infection disrupts energy metabolism in SCs remains unclear. This study aimed to determine the role of serum exosomes of HBV-infected patients in SC viability and glycolysis. Serum exosomes were obtained from 30 patients with (HBV+_exo) or without (HBV-_exo) HBV infection using high-speed centrifugation and identified by transmission electron microscopy and western blot analysis. Cell viability is determined by CCK-8 assay. Glycolysis is determined by detecting extracellular acidification rate and ATP levels. miR-122-5p expression levels are detected by quantitative RT-PCR, and a dual-luciferase gene reporter assay confirms the downstream target gene of miR-122-5p. Protein expression is determined by western blot analysis. The results show that HBV+ _exo inhibited cell viability, extracellular acidification rate, and ATP production of SCs. miR-122-5p is highly expressed in HBV+ _exo compared with that in HBV-_exo. Furthermore, HBV+ _exo is efficiently taken up by SCs, whereas miR-122-5p is efficiently transported to SCs. miR-122-5p overexpression downregulates ALDOA expression and inhibits SC viability and glycolysis. However, ALDOA overexpression reverses the effects of miR-122-5p and HBV+ _exo on SC viability and glycolysis. HBV+ _exo may deliver miR-122-5p to target ALDOA and inhibit SC viability and glycolysis, thus providing new therapeutic ideas for treating HBV-associated male infertility., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

BRD7 was identified as a tumor suppressor in nasopharyngeal carcinoma (NPC). Circular RNAs (CircRNAs) are involved in the occurrence and development of NPC as oncogenes or tumor suppressors. However, the function and mechanism of the circular RNA forms derived from BRD7 in NPC are not well understood. In this study, we first identified that circBRD7 was a novel circRNA derived from BRD7 that inhibited cell proliferation, migration, invasion of NPC cells, as well as the xenograft tumor growth and metastasis in vivo. Mechanistically, circBRD7 promoted the transcriptional activation and expression of BRD7 by enhancing the enrichment of histone 3 lysine 27 acetylation (H3K27ac) in the promoter region of its host gene BRD7, and BRD7 promoted the formation of circBRD7. Therefore, circBRD7 formed a positive feedback loop with BRD7 to inhibit NPC development and progression. Moreover, restoration of BRD7 expression rescued the inhibitory effect of circBRD7 on the malignant progression of NPC. In addition, circBRD7 demonstrated low expression in NPC tissues, which was positively correlated with BRD7 expression and negatively correlated with the clinical stage of NPC patients. Taken together, circBRD7 attenuates the tumor growth and metastasis of NPC by forming a positive feedback loop with its host gene BRD7, and targeting the circBRD7/BRD7 axis is a promising strategy for the clinical diagnosis and treatment of NPC., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Osteoarthritis (OA) is a common disease with a complex pathology. This study aimed to investigate the correlation between the aberrant upregulation of miR-181b and ferroptosis in chondrocytes during the progression of OA., Methods: An OA cell model was constructed with erastin. Ferrostatin-1 (Fer), bioinformatics, and dual-luciferase activity reports were used to investigate the effect of miR-181b on OA. Finally, a rat model of OA was induced by monosodium iodoacetate to verify that miR-181b inhibits SLC7A11 gene expression and increases ferroptosis., Results: The results showed that Fer could effectively reverse the erastin-induced inhibition of human chondrocyte viability, increase the level of collagenous proteins in human chondrocytes, and inhibit oxidative stress and ferroptosis. MiR-181b is abnormally elevated in OA cell models. Transfection of a miR-181b inhibitor could increase the expression levels of the ferroptosis-related proteins solute carrier family 7 members 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), thereby inhibiting the occurrence of ferroptosis in chondrocytes. In addition, hsa-miR-181b-5p and SLC7A11 have a targeted regulatory effect. Transfection of SLC7A11 siRNA effectively abrogated the increase in chondrocyte viability induced by the miR-181 inhibitor and increased ferroptosis. Finally, miR-181b was shown to exacerbate OA disease progression by inhibiting SLC7A11 gene expression and increasing ferroptosis in a rat OA model., Conclusions: Elevating miR-181b may mediate chondrocyte ferroptosis by targeting SLC7A11 in OA., (© 2023. The Author(s).)

Intervertebral disc degeneration (IDD) is characterised by nucleus pulposus (NP) loss and extracellular matrix (ECM) degeneration. Circular RNAs (circRNAs) have been reported to be dysregulated during IDD progression. Recently, reports showed that hsa_circ_0040039 was increased in degenerated lumbar disc samples. The aim of this study was to explore the specific role and underlying mechanisms of hsa_circ_0040039 in IDD. The expression of hsa_circ_0040039 was investigated in NP tissues of IDD patients. IL-1β was used to treat NP cells to construct an IDD in vitro model. Overexpression and loss-of-function assays and bioinformatic analysis were performed to evaluate the role and potential mechanism of hsa_circ_0040039 during IDD progression. Hsa_circ_0040039 expression was increased about 2 folds in NP tissues compared with normal tissues and IL-1β-stimulated NP cells also presented hsa_circ_0040039 upregulation, and its overexpression promoted cell proliferation and ECM degeneration. The depletion of hsa_circ_0040039 had the opposite effects. Based on bioinformatics prediction, Luciferase assay, PCR and Western blot, our study verified that hsa_circ_0040039 directly bond to miR-146b-3p, then mediated its targeted MMP2 and PCNA. Moreover, the overexpression of miR-146b-3p and the silence of MMP2 or PCNA, partially abolished the effect of hsa_circ_0040039 on IL-1β-stimulated NPs. Hsa_circ_0040039 may participate in IDD development by mediating the repair and regeneration of NPs through upregulation MMP2 and PCNA mediated by miR-146b-3p., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diabetic cardiomyopathy (DCM), a common complication of diabetes, is defined as ventricular dysfunction in the absence of underlying heart disease. Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), play a crucial role in the development of DCM. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify key modules in DCM-related pathways. DCM-related miRNA-mRNA network and DCM-related ceRNA network were constructed by miRNA-seq to identify hub genes in these modules. We identified five hub genes that are associated with the onset of DCM, including Troponin C1 (Tnnc1), Phospholamban (Pln), Fatty acid binding proteins 3 (Fabp3), Popeye domain containing 2 (Popdc2), and Tripartite Motif-containing Protein 63 (Trim63). miRNAs that target the hub genes were mainly involved in TGF-β and Wnt signaling pathways. GO BP enrichment analysis found these miRNAs were involved in the signaling of TGF-β and glucose homeostasis. Q-PCR results found the gene expressions of Pln, Fabp3, Trim63, Tnnc1, and Popdc2 were significantly increased in DCM. Our study identified five hub genes (Tnnc1, Pln, Fabp3, Popdc2, Trim63) whose associated ceRNA networks are responsible for the onset of DCM., (© 2023. The Author(s).)

Background: Peritoneal metastasis (PM) is an independent prognostic factor in gastric cancer (GC), however, the underlying mechanisms of PM occurrence remain unclear., Method: The roles of DDR2 were investigated in GC and its potential relationship to PM, and orthotopic implants into nude mice were performed to assess the biological effects of DDR2 on PM., Results: Herein, DDR2 level is more significantly observed to elevate in PM lesion than the primary lesion. GC with DDR2-high expression evokes a worse overall survival (OS) in TCGA, similar results of the gloomy OS with high DDR2 levels are clarified via the stratifying stage of TNM. The conspicuously increased expression of DDR2 was found in GC cell lines, luciferase reporter assays verified that miR-199a-3p directly targeted DDR2 gene, which was correlated to tumor progression. We ulteriorly observed DDR2 participated in GC stemness maintenance via mediating pluripotency factor SOX2 expression and implicated in autophagy and DNA damage of cancer stem cells (CSCs). In particular, DDR2 dominated EMT programming through recruiting NFATc1-SOX2 complex to Snai1 in governing cell progression, controlling by DDR2-mTOR-SOX2 axis in SGC-7901 CSCs. Furthermore, DDR2 promoted the tumor peritoneal dissemination in gastric xenograft mouse model., Conclusion: Phenotype screens and disseminated verifications incriminating in GC exposit the miR-199a-3p-DDR2-mTOR-SOX2 axis as a clinically actionable target for tumor PM progression. The herein-reported DDR2-based underlying axis in GC represents novel and potent tools for studying the mechanisms of PM., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Circular RNAs (circRNAs) are a novel type of endogenous non-coding RNAs, which are covalently closed loop structures formed by precursor mRNAs (pre-mRNAs) through back-splicing. CircRNAs are abnormally expressed in many tumors, and play critical roles in a variety of tumors as oncogenes or tumor suppressor genes by sponging miRNAs, regulating alternative splicing and transcription, cis-regulating host genes, interacting with RNA binding proteins (RBPs) or encoding polypeptides. Among them, the regulation of circRNAs on their corresponding host genes is a critical way for circRNAs to exit their functions. Accumulating evidence suggests that circRNAs are able to regulate the expression of host genes at the transcriptional level, post-transcriptional level, translational level, post-translational level, or by encoding polypeptides. Therefore, this paper mainly summarized the roles and association of circRNAs and their corresponding host genes in tumorigenesis and tumor progression, generalized the circRNAs that function synergistically or antagonistically with their host genes, and elaborated the mechanisms of mutual regulation between circRNAs and their host genes. More importantly, this review provides specific references for revealing the potential application of circRNAs combined with their host genes in tumor diagnosis, treatment and prognosis., (© 2023. The Author(s).)

Besides genetic alterations, the cellular environment also determines disease onset and progression. When different cell types contribute to disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes of psoriatic skin, and we show that expression in keratinocytes is induced by limited glucose availability and enables increased survival under limiting glucose conditions by increasing glutamine metabolism. In addition, miR-31 expression results in not only secretion of specific metabolites (aspartate and glutamate) but also secretion of immunomodulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibitors of miR31-induced metabolic rewiring and metabolic crosstalk with immune cells alleviate psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)

Aim: This study aimed to identify autophagy-related genes (ARGs) associated with non-obstructive azoospermia and explore the underlying molecular mechanisms., Methods: Two datasets associated with azoospermia were downloaded from the Gene Expression Omnibus database, and ARGs were obtained from the Human Autophagy-dedicated Database. Autophagy-related differentially expressed genes were identified in the azoospermia and control groups. These genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction (PPI) network, and functional similarity analyses. After identifying the hub genes, immune infiltration and hub gene-RNA-binding protein (RBP)-transcription factor (TF)-miRNA-drug interactions were analyzed., Results: A total 46 differentially expressed ARGs were identified between the azoospermia and control groups. These genes were enriched in autophagy-associated functions and pathways. Eight hub genes were selected from the PPI network. Functional similarity analysis revealed that HSPA5 may play a key role in azoospermia. Immune cell infiltration analysis revealed that activated dendritic cells were significantly decreased in the azoospermia group compared to those in the control groups. Hub genes, especially ATG3 , KIAA0652 , MAPK1 , and EGFR were strongly correlated with immune cell infiltration. Finally, a hub gene-miRNA-TF-RBP-drug network was constructed., Conclusion: The eight hub genes, including EGFR , HSPA5 , ATG3 , KIAA0652 , and MAPK1 , may serve as biomarkers for the diagnosis and treatment of azoospermia. The study findings suggest potential targets and mechanisms for the occurrence and development of this disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhong, Zhao, Deng, Wu, Zhu, Yang, Liu, Luo, Ma and Li.)

Background: Multiple studies have established a strong relationship between circRNA and cancer progression. Cervical lymph node metastasis is a key factor influencing the surgical approach and distant metastasis of papillary thyroid cancer (PTC). However, the role of circNDST1 in PTC has not been investigated. Our research focused on revealing the function and mechanism of action of circNDST1 in PTC., Methods: High-throughput sequencing and qPCR were used to assess the expression of circRNA in PTC tissues with extensive cervical lymph node metastasis and circNDST1 in cell lines, respectively. The proliferative effects of circNDST1 in vitro and in vivo were analyzed using CCK8, clone formation assay, EdU, and nude mouse tumorigenesis assay. The transwell scratch assay was employed in the scrutiny of the effect of circNDST1 on the migration and invasion abilities of thyroid cancer cells, while circNDST1's influence on the PI3K-Akt pathway and the Epithelial-Mesenchymal Transition (EMT) key protein expression was evaluated utilizing RNA sequencing and western blot. RNA pull-down and RIP were used to examine the binding of circNDST1 to CSNK2A1., Results: CircNDST1 was highly expressed in PTC cell lines, but knocking it down inhibited the proliferation, migration, and invasive abilities of TPC1 and KTC1 cell lines. CircNDST1 bonded with CSNK2A1 and promoted the interaction between CSNK2A1 and Akt, leading to the activation of the PI3K-Akt pathway and EMT., Conclusion: CircNDST1's high expression boosted thyroid cancer progression through the activation of the PI3K-Akt pathway and EMT in a CSNK2A1-dependent manner., (© 2022. The Author(s).)

Purpose: Diabetic wound is a highly prevalent and refractory disease. Extensive studies have confirmed that keratinocytes and macrophages play an important role in the process of wound healing. Additionally, exosomes are regarded as a vital intercellular communication tool. This study aimed to investigate the role of human keratinocyte-derived exosomal MALAT1 in the treatment of diabetic wound by influencing the biological function of macrophages., Methods: We mainly assessed the function of MALAT1 on the biological changes of macrophages, and the expression of MALAT1 in the keratinocyte-exosomes analyzed by quantitative real-time polymerase chain reaction (RT-qPCR). The downstream interaction between RNAs or proteins was assessed by mechanistic experiments. Besides, we evaluated the effects of human keratinocyte-derived exosomal MALAT1 on diabetic wound healing in vivo to verify in vitro results., Results: We demonstrated that human keratinocyte-derived exosomal MALAT1 enhanced the biological functions of high glucose-injured macrophages, including phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. Mechanistically, MALAT1 accelerated the expression of MFGE8 by competitively binding to miR-1914-3p, thereby affecting the function of macrophages and the signal axis of TGFB1/SMAD3, and finally promoting the healing of diabetic wounds. Human keratinocyte-derived exosomal MALAT1 might promote collagen deposition, ECM remodeling, and expression of MFGE8, VEGF, and CD31 but reduce the expression of TGFB and SMAD3 in an in vivo model of diabetic mice wounds, which accelerated diabetic wound healing and restored its function., Conclusion: The current study revealed that human keratinocyte-derived exosomal MALAT1 would suppress miR-1914-3p to activate MFGE8 and eventually promote wound healing by enhancing macrophage phagocytosis, converting to a pro-healing phenotype and reducing apoptosis. It proposed that keratinocyte-derived exosomes might have the capacity to serve as a new method for the clinical treatment of diabetic wound., Competing Interests: All authors declare no conflicts of interest in this work., (© 2023 Kuang et al.)

Deregulation of Pol III products causes a range of diseases, including neural diseases and cancers. However, the factors and mechanisms that modulate Pol III-directed transcription remain to be found, although massive advances have been achieved. Here, we show that STAT3 positively regulates the activities of Pol III-dependent transcription and cancer cell growth. RNA-seq analysis revealed that STAT3 inhibits the expression of TP73, a member of the p53 family. We found that TP73 is not only required for the regulation of Pol III-directed transcription mediated by STAT3 but also independently suppresses the synthesis of Pol III products. Mechanistically, TP73 can disrupt the assembly of TFIIIB subunits and inhibit their occupancies at Pol III target loci by interacting with TFIIIB subunit TBP. MiR-106a-5p can activate Pol III-directed transcription by targeting the TP73 mRNA 3' UTR to reduce TP 73 expression. We show that STAT3 activates the expression of miR-106a-5p by binding to the miRNA promoter, indicating that the miR-106a-5p links STAT3 with TP73 to regulate Pol III-directed transcription. Collectively, these findings indicate that STAT3 functions as a positive regulator in Pol III-directed transcription by controlling the miR-106a-5p/TP73 axis., Competing Interests: CZ, SZ, HD, SZ, JW, XS, DY, YZ, WD No competing interests declared, (© 2023, Zhang et al.)

Circular RNAs (circRNAs) are novel noncoding RNAs with covalently closed-loop structures that can regulate eukaryotic gene expression. Due to their stable structure, circRNAs are widely distributed in the cytoplasm and have important biological functions, including as microRNA sponges, RNA-binding protein conjugates, transcription regulators, and translation templates. Breast cancer is among the most common malignant cancers diagnosed in women worldwide. Despite the development of comprehensive treatments, breast cancer still has high mortality rates. Recent studies have unmasked critical roles for circRNAs in breast cancer as regulators of tumour initiation, progression, and metastasis. Further, research has revealed that some circRNAs have the potential for use as diagnostic and prognostic biomarkers in clinical practice. Herein, we review the biogenesis and biological functions of circRNAs, as well as their roles in different breast cancer subtypes. Moreover, we provide a comprehensive summary of the clinical significance of circRNAs in breast cancer. CircRNAs are believed to be a hot focus in basic and clinical research of breast cancer, and innovative future research directions of circRNAs could be used as biomarkers, therapeutic targets, or novel drugs. Abbreviations: CeRNA: Competitive endogenous RNA; ciRNA: Circular intronic RNA; circRNA: Circular RNA; EIciRNA: Exon-intron circRNA; EMT: Epithelial-mesenchymal transition; IRES: Internal ribosome entry site; lncRNA: Long non-coding RNA; miRNA: MicroRNA; MRE: MiRNA response element; ncRNA: Non-coding RNA; RBP: RNA-binding protein; RNA-seq: RNA sequencing; RT-PCR: Reverse transcription-polymerase chain reaction.

Background: Psoriasis is an immune-mediated skin disorder caused by the proliferation of keratinocytes. Although psoriasis is generally diagnosed based on clinical manifestations, sensitive biomarkers are needed to help diagnose psoriasis early with atypical presentations. MicroRNAs play a functional role in the development of psoriasis, and they are stable and suitable as biomarkers in psoriasis., Material and Methods: The GSE50790 and GSE53552 datasets from the Gene Expression Omnibus (GEO) database were used to identify Differentially Expressed Genes (DEGs) between the control group and the lesional group. DEGs were processed for enrichment analysis to explore the functions, and a Protein-Protein Interaction (PPI) network was constructed to obtain gene clusters. The signalling pathway associated with gene cluster 1 was processed to further identify related genes. Hub genes were obtained through the intersection of cluster 1 and the related genes. Hub genes were used to predict the miRNAs through a gene-miRNA interaction network. The relative expression of miRNAs was measured by qRT-PCR to identify the suitability of miRNAs as biomarkers., Results: Bioinformatics analysis revealed that the chemokine signalling pathway is involved in the development of psoriasis. Five related miRNAs were mined from the datasets, and qRT-PCR showed that hsa-miR-612 (p=0.0015), hsa-miR-3194-5p (p=0.0078) and hsa-miR-4316 (p<0.0001) may be potential biomarkers in psoriasis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: This study aimed to verify miRNAs and the molecular mechanisms of diagnostic and prognostic biomarkers for rectal adenocarcinoma., Methods: Two miRNA datasets of rectal adenocarcinoma were obtained from GEO and TCGA. GEO2R tool, Venn diagram, Kaplan-Meier survival analysis, KEGG pathway analyses, DIANA TOOLS, and Wilcoxon rank-sum test were used for biological information analysis. The diagnostic utility of miRNAs and immune infiltration of tumors in Chinese patients were validated by RTqPCR and immunofluorescence analysis., Results: MiR-21-5P and miR-455-5p were both found to have a significant correlation with poor prognosis and higher expression in rectal adenocarcinoma. Besides, the ability to prognosis was independent of the clinicopathological stage. MiR-21-5P and miR-455-5p were enriched in the TGF-beta, Wnt, MAKP, and PI3K-AKT signaling pathways. Meanwhile, the high expression phenotype of miR-21-5P and miR-455-5p decreased CD4 + and CD8 + T cells., Conclusion: In summary, we found two significant diagnostic and prognostic miRNAs of rectal adenocarcinoma via integrated bioinformatics approach and clinical trials, which might decrease CD4 + and CD8 + T cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this study, we aimed to expand the current miRNA data bank of Chinese fir ( Cunninghamia lanceolata (Lamb.) Hook.) regarding its potential value for further genetic and genomic use in this species. High-throughput small RNA sequencing successfully captured 140 miRNAs from a Chinese fir selfing family harboring vigor and depressed progeny. Strikingly, 75.7% (n = 106) of these miRNAs have not been documented previously, and most (n = 105) of them belong to the novel set with 6858 putative target genes. The new datasets were then integrated with the previous information to gain insight into miRNA genetic architecture in Chinese fir. Collectively, a relatively high proportion (62%, n = 110) of novel miRNAs were found. Furthermore, we identified one MIR536 family that has not been previously documented in this species and four overlapped miRNA families (MIR159, MIR164, MIR171&#95;1, and MIR396) from new datasets. Regarding the stability, we calculated the secondary structure free energy and found a relatively low R 2 value (R 2 < 0.22) between low minimal folding free energy (MFE) of pre-miRNAs and MFE of its corresponding mature miRNAs in most datasets. When in view of the conservation aspect, the phylogenetic trees showed that MIR536 and MIR159 sequences were highly conserved in gymnosperms.

Hepatocellular carcinoma (HCC) is one of the most common and lethal types of cancer. This study aimed to identify the expression regulatory network and a prognostic signature of HCC. RNA-seq data from The Cancer Genome Atlas were used to identify the differentially expressed genes (DEGs) between HCC and normal liver tissues. DEGs were subjected to the construction of protein-protein interaction (PPI) network and enrichment analysis of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. The results showed that most of the DEGs were enriched in the cell cycle pathway, and the top 10 hub genes in the PPI network belong to the cell cycle pathway. A ceRNA network was constructed using starBase database, including one lncRNA (SNHG1), seven miRNAs (miR-195-5p, miR-199a-3p, miR-199a-5p, miR-199b-3p, miR-383-5p, miR-424-5p and miR-654-3p) and six of the top 10 hub genes (BUB1, CCNA2, CCNB1, KIF11, NCAPG, and TOP2A). In vitro experiments showed that knockdown of SNHG1 in the HCC cell lines (Huh7 and HepG2) decreased the expression of the six hub genes and cell viability, leading to cell cycle arrest at the G1 phase. These findings indicate that SNHG1 promotes cell proliferation by regulating cell cycle-related genes as a ceRNA. Additionally, Kaplan-Meier's survival and multivariate Cox regression analysis identified a prognostic signature of seven genes (including SNHG1 and the six SNHG1-regulated hub genes) for overall survival of HCC patients. In conclusion, this study identified a novel regulatory network in HCC and a potential independent prognostic factor for overall survival of HCC patients.

Activation of an innate immune response serves as a key, contributing factor in perinatal brain injury. The current study sought to evaluate the clinical significance of innate defense regulatory peptide 1018 (IDR-1018)-derived peptide mediating ceRNA regulation network as a biomarker in neonatal mice with hypoxic-ischemic brain damage (HIBD). Firstly, bioinformatics analyses were performed to screen the HIBD-related candidate genes, miRNAs, and lncRNAs. The StarBase, miRDB, and LncBase databases were retrieved to obtain the lncRNA-miRNA-mRNA network, which revealed the ceRNA regulatory network mediated by IDR-1018. Subsequently, RT-qPCR was adopted to determine the expression patterns of MIAT, miR-7a-5p, and Plp2 in neonatal mice with HIBD after treatment with IDR-1018. Moreover, the relationship among mRNA, miRNA, and lncRNA in primary hippocampal neurons was verified by means of dual-luciferase reporter assay and RIP assay. Initial findings demonstrated that Plp2, mmu-miR-7a-5p, and three lncRNAs (MIAT, XIST, and 1700020I14RIK) were related to HIBD. Moreover, IDR-1018 could relieve HIBD in neonatal mice. Plp2 and MIAT were down-regulated, while mmu-miR-7a-5p was up-regulated in the striatum, hippocampus, and cortical tissues of the neonatal mice with HIBD, whereas treatment with the IDR-1018 could revere these trends. Additionally, MIAT acted as a ceRNA of miR-7a-5p to elevate Plp2 expression. In conclusion, our findings highlighted that IDR-1018 relieved HIBD in neonatal mice via the MIAT/miR-7a-5p/Plp2 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 © 2022 Elsevier Inc. All rights reserved.)

Objectives: Pancreatic cancer (PC) is one of the most deadly malignancies in the world. Recently, circular RNAs play crucial roles in PC progression. However, the functions of circ&#95;0058058 in PC are barely known., Methods: The expression of circ&#95;0058058, microRNA-557-5p (miR-557), and programmed cell death receptor ligand 1 (PDL1) was detected by quantitative real-time polymerase chain reaction. Functional experiments were implemented to disclose the effect of circ&#95;0058058 deficiency on PC cell proliferation, apoptosis, invasion, angiogenesis, and immune escape. The binding relationship between miR-557 and circ&#95;0058058 or PDL1 was identified by dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo assay was used to disclose the impact of circ&#95;0058058 silencing on tumor formation in vivo., Results: Circ&#95;0058058 was highly expressed in PC tissues and cell lines. Knockdown of circ&#95;0058058 repressed cell proliferation, invasion, angiogenesis, and immune escape while contributed to apoptosis in PC cells. Mechanically, circ&#95;0058058 worked as a molecular sponge of miR-557 to regulate PDL1 expression. Moreover, circ&#95;0058058 showed a promotional effect on tumor growth in vivo., Conclusions: Our findings suggested that circ&#95;0058058 served as miR-557 sponge to upregulate PDL1, thereby triggering PC proliferation, invasion, angiogenesis, and immune escape., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Investigating the long-term effects of microplastics (MPs) in vivo is necessary for evaluating its biological toxicity. Previously, we showed that MPs elicit vascular dysfunctions in atherosclerotic mice. However, the effects of long-term treatment with environmental levels of MPs on biological functions and RNA expression profiles in wild-type mice are unknown. Here, C57BL/6 mice were administered 1000 μg/L MPs through their drinking water for 180 days. Transcriptomic analyses, biochemical analysis, and histopathological examination were conducted to determine the key signals and molecular mechanisms triggered by MPs in vivo using whole transcriptome sequencing, enzyme-linked immunosorbent assay, and histopathological analysis. Notably, our data revealed that MPs aggravated vascular lesions and organ injuries, particularly liver, kidney, and heart injuries. Additionally, MPs exacerbated oxidative injuries by inhibiting the activities of antioxidant enzymes and increasing the levels of the serum biochemistry indicator of organ damage. RNA sequencing of vascular tissues showed that 674 mRNAs, 39 lncRNAs, 196 miRNAs, and 565 circRNAs were abnormally expressed in MPs-treated mice compared with the untreated group. Pathway enrichment analyses identified pathways linked to the toxicity of MPs, including lysosomal, NOD-like receptor, and peroxisome proliferator-activated receptor pathways. Additionally, competing endogenous RNA networks were constructed and hub RNAs were identified using bioinformatics analysis. Taken together, our data suggested that toxicity induced by long-term exposure to MPs continually presents with extensive changes in biological features and global gene expression profiles. Our data provides new insights into the biological toxicity of MPs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Circular RNAs (circRNAs) are a type of endogenous non-coding RNA and a critical epigenetic regulation way that have a closed-loop structure and are highly stable, conserved, and tissue-specific, and they play an important role in the development of many diseases, including tumors, neurological diseases, and cardiovascular diseases. CircSMARCA5 is a circRNA formed by its parental gene SMARCA5 via back splicing which is dysregulated in expression in a variety of tumors and is involved in tumor development with dual functions as an oncogene or tumor suppressor. It not only serves as a competing endogenous RNA (ceRNA) by binding to various miRNAs, but it also interacts with RNA binding protein (RBP), regulating downstream gene expression; it also aids in DNA damage repair by regulating the transcription and expression of its parental gene. This review systematically summarized the expression and characteristics, dual biological functions, and molecular regulatory mechanisms of circSMARCA5 involved in carcinogenesis and tumor progression as well as the potential applications in early diagnosis and gene targeting therapy in tumors.

Objective: To investigate whether miR-125b-5p regulates biological behaviors of ovarian cancer cells by targeted regulation of CD147 expression., Methods: RT-qPCR was used to detect the expression of miR-125b-5p and CD147 mRNA in ovarian cancer tissues and cancer cell lines. SKOV3 cells transfected with miR-125b-5p mimic and HO8910 cells transfected with miR-125b-5p inhibitor were examined for changes in proliferation, migration and invasion using CCK-8 assay, colonyforming assay and Transwell assay. Starbase was used to predict the potential binding sites between miR-125b-5p and CD147, and double luciferase reporter gene assay was used to verify the targeting relationship. In SKOV3 cells, the effects of cotransfection with miR-125b-5p mimic and pcDNA3.1-CD147 (or pcDNA3.1) plasmid on cell proliferation, migration and invasion were assessed with CCK-8 assay and Transwell assay., Results: The expression of miR-125b-5p was significantly lowered and that of CD147 was increased in both ovarian cancer tissues and ovarian cancer cell lines ( P < 0.05). Overexpression of miR-125b-5p in SKOV3 cells resulted in significantly suppressed cell proliferation, migration and invasion, while downregulation of miR-125b-5p in HO8910 cells promoted cell proliferation, migration and invasion. Bioinformatic analysis predicted that miR-125b-5p binds to CD147, which was confirmed by luciferase reporter gene assay. RT-qPCR and Western blotting showed that miR-125b-5p negatively regulated CD147 expression ( P < 0.05). In SKOV3 cells, the inhibitory effects of miR-125b-5p mimic on cell proliferation, invasion and migration were significantly attenuated by co-transfection of the cells with pcDNA3.1-CD147 plasmid., Conclusion: miR-125b-5p inhibits the migration and invasion of ovarian cancer cells by negatively regulating the expression of CD147.

BACKGROUND : Circular RNAs (circRNAs) are covalently closed single-stranded RNAs with multiple biological functions. CircRNA.0007127 is derived from the carbon catabolite repression 4-negative on TATA-less ( CCR4-NOT ) complex subunit 2 ( CNOT2 ), which was found to regulate tumor cell apoptosis through caspase pathway. METHODS : Potential circRNA.0007127 target microRNAs (miRNAs) were analyzed by miRanda, TargetScan, and RNAhybrid software, and the miRNAs with binding sites for apoptosis-related genes were screened. The roles of circRNA.0007127 and its downstream target, microRNA (miR)‍-513a-5p, were validated by quantitative real-time polymerase chain reaction (qPCR), flow cytometry, mitochondrial membrane potential, immunofluorescence, western blot, and caspase-8 (CASP8) protein activity in vitro in H 2 O 2 -induced K-562 cells. The circRNA.‍0007127‍‒‍miR-513a-5p and CASP8‍ ‒‍miR-513a-5p interactions were verified by luciferase reporter assays. RESULTS : Silencing circRNA.0007127 decreased cell apoptosis by inhibiting CASP8 pathway activation in K-562 cells. Compared with the control group, the expression of CASP8 was reduced by 50% and the 43-kD fragment of CASP8 protein was significantly reduced ( P ≤0.05). The luciferase reporting assay showed that circRNA.0007127 combined with miR-513a-5p or CASP8 , with extremely significant differences ( P ≤0.001). The overexpression of miR-513a-5p inhibited the gene expression level of CASP8 in a human myeloid leukemia cell model (75% change) and the level of a 43-kD fragment of CASP8 protein ( P ≤0.01). The rescue experiment showed that cotransfection with circRNA.0007127 small-interfering RNA (siRNA) and the miR-513a-5p inhibitor increased CASP8 gene expression and the apoptosis rate, suggesting that the miR-513a-5p inhibitor is a circRNA.0007127 siRNA antagonist. CONCLUSIONS : CircRNA.0007127 regulates K-562 cell apoptosis through the miR-513a-5p/ CASP8 axis, which can serve as a novel powerful molecular target for K-562 cells.

Object. β -Elemene is an emerging antitumor Chinese medicine, but the exact mechanism of action of β -elemene in colorectal cancer (CRC) remains unclear. This study aimed to explore the mechanism of the lncRNA-miRNA-mRNA network in the process of β -elemene inhibiting CRC. Methods . RNA sequencing was performed on CRC cells from the control group (untreated) and the case group ( β -elemene-treated). According to the sequencing data, we screened the differentially expressed (DE) lncRNAs, miRNAs, and mRNAs and then analyzed them by functional enrichment analyses. Through the lncRNA-miRNA-mRNA network, the key miRNAs and mRNAs involved in the process of β -elemene inhibiting CRC were further identified. Results . Totally, 607 upregulated and 599 downregulated DElncRNAs, 12 downregulated and 24 upregulated DEmiRNAs, and 3153 downregulated and 3248 upregulated DEmRNAs were identified. Through the lncRNA-miRNA-mRNA network, 3 miRNAs (miR-7109-3p, miR-4506, and miR-3182), 7 prognostic mRNAs (ALPG, DTX1, HOXD13, RIMS3, SLC16A8, SYT1, and TNNT1), and 2 key mRNAs (RIMS3 and SLC16A8) were determined to participate in the inhibitory mechanism of β -elemene in CRC. Conclusion . This study revealed for the first time that the lncRNA-miRNA-mRNA network is involved in the regulation of β -elemene in CRC, and these identified miRNAs and mRNAs could be new clinical prognostic biomarkers and therapeutic targets for CRC patients., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Heng Deng et al.)

Long noncoding RNA (lncRNA) plays a crucial role in the pathogenesis of various diseases, including colorectal cancer (CRC). The gene mutations of adenomatous polyposis coli (APC) were found in most patients with CRC. They function as important inducers of tumorigenesis. Based on our microarray results, we identified a specific upregulated lncRNA in CRC (SURC). Further analysis showed that high SURC expression correlated with poorer disease-free survival and overall survival in patients with CRC. Furthermore, we found that mutated APC genes can promote the transcription of SURC by reducing the degradation of β-catenin protein in CRC. Functional assays revealed that knockdown of SURC impaired CRC cell proliferation, colony formation, cell cycle, and tumor growth. Additionally, SURC promotes CCND2 expression by inhibiting the expression of miR-185-5p in CRC cells. In conclusion, we demonstrate that SURC is a specific upregulated lncRNA in CRC and the SURC/miR-185-5p/CCND2 axis may be targetable for CRC diagnosis and therapy.

Introduction: Hepatocellular carcinoma (HCC) is a subtype of primary liver cancer and a major cause of death. Although miRNA plays an important role in hepatocellular carcinoma, the specific regulatory network remains unclear. Therefore, this paper comprehensively describes the miRNA-related signaling pathways in HCC and the possible interactions among different signaling pathways. The aim is to lay the foundation for the discovery of new molecular targets and multi-target therapy., Areas Covered: Based on miRNA, HCC, and signaling pathways, the literature was searched on Web of Science and PubMed. Then, common targets between different signaling pathways were found from KEGG database, and possible cross-regulation mechanisms were further studied. In this review, we elaborated from two aspects, respectively, laying a foundation for studying the regulatory mechanism and potential targets of miRNA in HCC., Expert Opinion: Non-coding RNAs have become notable molecules in cancer research in recent years, and many types of targeted drugs have emerged. From the outset, molecular targets and signal pathways are interlinked, which suggests that signal pathways and regulatory networks should be concerned in basic research, which also provides a strong direction for future mechanism research.

Vascular calcification is one of the major complications of chronic kidney disease (CKD), which could be further accelerated by the osteogenic transition and apoptosis of smooth muscle cells, thereby advancing the progression of renal diseases and increasing the mortality rate of cardiovascular events. MicroRNA is a kind of key regulator in the phenotypic transition of vascular smooth muscle cells (VSMCs), but its role remains unclear in VSMCs. In this study, VSMCs were stimulated by platelet-derived growth factors - BB (PDGF-BB) in varying concentrations to establish the VSMC dysfunction models. The relative expression of miR-29a-5p was quantified via the quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation of VSMCs was determined via the BrdU method, analysis of cell cycle via flow cytometry, and the migration of VSMCs via Transwell assay. Expression of γ-secretase activating protein (GSAP) and markers of VSMC differentiation, including α-SMA, SM-22α, SMMHC and Calponin, was quantified via the Western blot. The targeting relationship between the 3'-UTR of miR-29a-5p and GSAP was validated through the dual-luciferase reporter gene assay. As a result, we found that PDGF-BB could trigger a decrease of miR-29a-5p in a time- and dose-dependent manner (P < 0.05). Overexpression of miR-29a-5p could curb the effect of PDGF-BB on the proliferation and migration of VSMCs while upregulating the expression of markers of differentiation (P < 0.05). In addition, the expression of GSAP was also affected by the negative regulation of miR-29a-5p, while the restoration of GSAP eliminated the effect of miR-29a-5p on the VSMCs partially (P < 0.05). Moreover, vascular calcification models were also established in the CKD rats, suggesting that the inhibition of GSAP could prevent PTH-induced vascular calcification in CKD rats. In conclusion, miR-29a-5p could inhibit the PDGF-BB-induced proliferation, migration and phenotypic transition of VSMCs via targeting GSAP. Thus, miR-29a-5p/GSAP might be a potential target for the treatment of vascular calcification.

tRNA-derived small RNAs (tsRNAs) participate in several biological processes, including carcinogenesis. The correlations between tsRNAs and human cancers are attracting substantial attention. Nevertheless, the involvement of tsRNAs in laryngeal squamous cell carcinoma (LSCC) progression remains unclear. We constructed tsRNAs expression profiles in LSCC and adjacent normal tissues by next-generation sequencing. Interestingly, we identified a specific 5'-tiRNA fragment (tRF-33-Q1Q89P9L842205) that was significantly downregulated and was closely associated with lymph node metastasis and advanced stages of LSCC. Importantly, we found that tRF-33-Q1Q89P9L842205 suppressed cell growth, proliferation, migration, invasion and induced apoptosis in LSCC by directly silencing phosphoinositide 3-kinase catalytic subunit (PIK3CD). We speculated that tRF-33-Q1Q89P9L842205 is a potential diagnostic biomarker for LSCC and acts as a tumor suppressor by directly targeting PIK3CD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Alzheimer disease (AD) is the leading cause of dementia that affects millions of old people. Despite significant advances in the understanding of AD pathobiology, no disease modifying treatment is available. MicroRNA-124 (miR-124) is the most abundant miRNA in the normal brain with great potency to ameliorate AD-like pathology, while it is deficient in AD brain. Herein, the authors develop a DNA nanoflowers (DFs)-based delivery system to realize exogenous supplementation of miR-124 for AD therapy. The DFs with well-controlled size and morphology are prepared, and a miR-124 chimera is attached via hybridization. The DFs are further modified with RVG29 peptide to simultaneously realize brain-blood barrier (BBB) penetration and neuron targeting. Meanwhile, Rutin, a small molecular ancillary drug, is co-loaded into the DFs structure via its intercalation into the double stranded DNA region. Interestingly, Rutin could synergize miR-124 to suppress the expression of both BACE1 and APP, thus achieving a robust inhibition of amyloid β generation. The nanosystem could pro-long miR-124 circulation in vivo, promote its BBB penetration and neuron targeting, resulting in a significant increase of miR-124 in the hippocampus of APP/PS1 mice and robust therapeutic efficacy in vivo. Such a bio-derived therapeutic system shows promise as a biocompatible nanomedicine for AD therapy., (© 2022 Wiley-VCH GmbH.)

Osteoporosis (OP) is a systemic bone metabolic disease with complicated pathogenesis and is difficult to cure clinically. The regulatory mechanisms of OP are needed to be further investigated. In the present study, we focused on the role of myocardial infarction-associated transcript (MIAT) in OP development and examined the underlying mechanism. The serum expression levels of MIAT in samples from patients with OP and healthy controls were compared using quantitative reverse transcription-PCR (qRT-PCR). The dual-luciferase reporter assay was used to confirm the relationship between MIAT and its potential target microRNA, i.e., miR-150-5p. Moreover, bone marrow-derived mesenchymal stem cells (BMSCs) were cultured and transfected with MIAT shRNA, with or without miR-150-5p inhibitor. EdU staining and colony formation analysis were performed to determine the proliferation ability of these cells. Furthermore, the TUNEL assay and flow cytometry were used to assess BMSC apoptosis. Finally, RT-PCR and Western blot assays were employed to assess the expression of osteogenic differentiation biomarkers. Compared with controls, the expression of MIAT was significantly increased, whereas that of miR-150-5p was markedly decreased in patients with OP. MIAT and miR-150-5p expression levels exhibited a strong negative correlation. Furthermore, osteogenic differentiation indicators were suppressed in serum of OP patients. MIAT was downregulated, and miR-150-5p was upregulated in induced to osteogenic differentiation BMSCs. Furthermore, downregulation of MIAT dramatically promoted osteogenic differentiation, increased proliferation, and inhibited apoptosis in BMSCs; miR-150-5p inhibitor abrogated the effects of MIAT. In conclusion, lncRNA MIAT can regulate the proliferation, apoptosis, and osteogenic differentiation of BMSCs.

MiRNAs are a class of small non-coding RNA molecules that play an important role in many biological processes, and determining miRNA-disease associations can benefit drug development and clinical diagnosis. Although great efforts have been made to develop miRNA-disease association prediction methods, few attention has been paid to in-depth classification of miRNA-disease associations, e.g. up/down-regulation of miRNAs in diseases. In this paper, we regard known miRNA-disease associations as a signed bipartite network, which has miRNA nodes, disease nodes and two types of edges representing up/down-regulation of miRNAs in diseases, and propose a signed graph neural network method (SGNNMD) for predicting deregulation types of miRNA-disease associations. SGNNMD extracts subgraphs around miRNA-disease pairs from the signed bipartite network and learns structural features of subgraphs via a labeling algorithm and a neural network, and then combines them with biological features (i.e. miRNA-miRNA functional similarity and disease-disease semantic similarity) to build the prediction model. In the computational experiments, SGNNMD achieves highly competitive performance when compared with several baselines, including the signed graph link prediction methods, multi-relation prediction methods and one existing deregulation type prediction method. Moreover, SGNNMD has good inductive capability and can generalize to miRNAs/diseases unseen during the training., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: To investigate the mechanisms employed by PS-T (polysaccharides of Trametes, PS-T), the main active ingredient of Huaier granules, to improve the susceptibility of hepatoma cells to oxaliplatin (OXA)., Methods: Cell proliferation in response to PS-T was determined both in vitro and in vivo. The effects of PS-T on miRNAs were analyzed with the use of a microarray. MiRNAs were screened under specific conditions (P < .05, log FoldChange  > ABS [1.5]) and further silenced or overexpressed by liposome transfection. Levels of ABCB1 mRNA and P-gp were detected by qRT-PCR and western blot analysis, respectively. A dual fluorescence assay was performed to determine whether miRNA directly targets ABCB1., Results: PS-T enhanced the inhibitory effect of OXA in human hepatoma cells and xenografts. Among 5 up-regulated miRNAs, overexpression of only miR-224-5p inhibited the expression of ABCB1 mRNA and P-gp, while silencing of miR-224-5p had an opposite effect. Moreover, miR-224-5p can directly target the 3'-UTR of ABCB1., Conclusion: PS-T increases the sensitivity of human hepatoma cells to OXA via the miR-224-5p/ABCB1/P-gp axis.

Glioma serves as the most common malignancy influencing modern people and is associated with severe morbidity and high mortality. Long non-coding RNAs (lncRNAs) as crucial regulators participate in multiple cancer progression. However, the role of lncRNA LINC01094 in the development of glioma remains unclear. Here, we aimed to explore the effect of lncRNA LINC01094 on the glioma progression and the underlying mechanism. Significantly, we revealed that the expression levels of LINC01094 were elevated in the glioma patient tissues compared to adjacent normal tissues. The LINC01094 expression was enhanced in the glioma cell lines. The depletion of LINC01094 inhibited cell viability and colony formation in the glioma cells. Meanwhile, the migration and invasion of glioma cells were impaired by the depletion of LINC01094. Mechanically, we identified that LINC01094 was able to sponge the miR-224-5p in the glioma cells and miR-224-5p inhibitor could reverse the effect of LINC01094 on glioma progression. In addition, miR-224-5p targeted CHSY1 and LINC01094 up-regulated CHSY1 by targeting miR-224-5p in the glioma cells. LINC01094 promoted glioma progression by the positive regulation of CHSY1. Moreover, tumorigenicity analysis showed that LINC01094 enhanced tumor growth of glioma in vivo. Thus, we conclude that lncRNA LINC01094 promotes glioma progression by modulating miR-224-5p/CHSY1 axis. Our finding provides new insights into the mechanism by which lncRNA LINC01094 contributes to the development of glioma, improving the understanding of lncRNA LINC01094 and glioma. LncRNA LINC01094, miR-224-5p, and CHSY1 may serve as potential targets for glioma., (© 2021. Japan Human Cell Society.)

Background: Aberrant expression of circular RNAs (circRNAs) during placental development could affect fetal growth and contribute to preeclampsia (PE). Circ&#95;0011460 was found to be differentially expressed in placental samples of PE. However, the exact function and mechanism of circ&#95;0011460 in PE process remain largely undefined., Methods: Levels of circ&#95;0011460, microRNA (miR)-762, and high-temperature requirement-A serine peptidase 1 (HTRA1) were detected using quantitative real-time polymerase chain reaction and Western blot. In vitro experiments in HTR8/SVneo cells were conducted using cell counting kit-8, wound healing, transwell, flow cytometry and Western blot assays. The direct interactions between miR-762 and circ&#95;0011460 or HTRA1 were verified using dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays., Results: Circ&#95;0011460 possessed a loop structure and was highly expressed in placental tissues of PE patients. Overexpression of circ&#95;0011460 greatly suppressed HTR8/SVneo cell proliferation, migration, and invasion, and accelerated cell apoptosis. While circ&#95;0011460 knockdown yielded the opposite trends on above biological behaviors. Mechanistically, we confirmed that circ&#95;0011460 could up-regulate HTRA1 expression via serving as a sponge of miR-762. Further rescue studies demonstrated that circ&#95;0011460 exerted its roles via targeting miR-762, and miR-762 promoted HTR8/SVneo cell growth, migration and invasion via regulating HTRA1., Conclusion: In all, circ&#95;0011460 suppressed HTR8/SVneo cell growth, migration, and invasion via miR-762/HTRA1 axis, suggesting a new insight into the pathogenesis of PE., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To explore the molecular mechanism for thyroid cancer metastasis via analyzing the role of microRNA (miR)-21-5p and its target gene recombinant sclerostin domain containing protein 1 (SOSTDC1) in thyroid cancer., Methods: The target miR-21-5p was screened through bioinformatics analysis and cell verification, and the thyroid cancer cell lines was transfected with miR-21-5p inhibitor. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test, flow cytometry, and cell scratch test were used to detect the proliferation, apoptosis and migration of thyroid cancer cells in the miR-21-5p inhibitor group and the inhibitor control group, respectively. The luciferase report experiment was used to verify the relationship between miR-21-5p and SOSTDC1, Western blotting was used to detect the expression levels and phosphorylation levels of SOSTDC1,phosphatidylinositol 3 kinase (PI3K), protein kinase B (Akt) and mitogen-activated protein kinases (MAPK), extracellular regulated protein kinases (ERK) in thyroid cancer cells., Results: MiR-21-5p was significantly increased in thyroid cancer cells,which was negatively correlated with SOSTDC1 ( r =-0.24, P <0.01). The proliferation and migration of thyroid cancer cells in the miR-21-5p inhibitor group was significantly lower than that in the inhibitor control group (both P <0.01), and the apoptosis rate in the miR-21-5p inhibitor group was significantly higher than that in the inhibitor control group ( P <0.01).The luciferase report experiment showed that miR-21-5p could target and regulate the expression level of SOSTDC1, and the expression of PI3K in the miR-21-5p inhibitor group was significantly lower than that in the inhibitor control group ( P <0.01). There were no significant changes in Akt and ERK1/2 levels, but the phosphorylation levels of Akt and ERK1/2 in the miR-21-5p inhibitor group were significantly lower than those in the inhibitor control group (both P <0.01)., Conclusions: MiR-21-5p in thyroid cancer cells can target the expression of SOSTDC1 and affect the activities of PI3K/Akt and MAPK/ERK, thereby inhibiting the apoptosis of thyroid cancer cells and promoting cell proliferation and migration.

MicroRNAs (miRNAs) are a class of evolutionarily conserved small non-coding RNAs that regulate gene expression at the translation level in cell growth, proliferation and differentiation. In addition, some types of miRNAs have been proven to be key modulators of both CNS development and plasticity, such as let-7, miR-9 and miR-124. In this research, we found miR-8b acts as an important regulator involved in brain and eyespot regeneration in Dugesia japonica. miR-8b was highly conserved among species and was abundantly expressed in central nervous system. Here, we detected the expression dynamics of miR-8b by qPCR during the head regeneration of D. japonica. Knockdown miR-8b by anti-MIRs method caused severe defects of eyes and CNS. Our study revealed the evolutionary conserved role of miR-8b in the planarian regeneration process, and further provided more research ideas and available information for planarian miRNAs., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Colorectal cancer (CRC) belongs to one of gastric cancers that half of cases will develop metastasis, causing higher mortality or chemotherapy resistance. In the present study, the long noncoding RNA zinc finger antisense 1 (ZFAS1) was proved to have high expression level in CRC samples and in advanced stages. Additionally, it also indicated that p53 status is associated with ZFAS1 expression. Silencing ZFAS1 reduced both migration and invasion ability of DLD-1 and HCT-116 cells, which is relevant to the EMT process. In addition, it was confirmed that miR-34b, a tumor suppressor miRNA directly targeted ZFAS1 3' untranslated region (3'UTR) and inhibited ZFAS1 expression. Furthermore, miR-34b partially reversed the effect of ZFAS1 on migration and invasion ability in DLD-1 cells. Meanwhile, p53 status changes by overexpression vectors or siRNA turbulent ZFAS1 expression. Besides, it was found that in most cases, the oncogene SOX4 was directly targeted by miR-34b and positive correlated to ZFAS1 expression. Silencing ZFAS1 induced SOX4 expression in DLD-1 cells. Our data demonstrated the functions and mechanisms of ZFAS1 in CRC metastasis, illustrating miR-34b directly targets ZFAS1 and inhibits metastasis ability of CRC cells. SOX4 is also the direct downstream target of miR-34b, and silencing ZFAS1 can inhibit SOX4 though modulating miR-34b.

Aims: This study investigated the effects of exercise and diet intervention on appetite-regulating hormones and subjective appetite changes in obese children and examined expressions of specific key microRNAs (miRNA, miR)., Methods: 16 obese children were included in a training program consisting of exercise and diet intervention for 6 weeks. Before and after the intervention, fasting blood was collected to determine appetite-regulating hormones (leptin, ghrelin, and orexin) and miRNA (miR-103a-3p and miR-200a-3p) levels; eating behavior of the children was reported using the Children Eating Behavior Questionnaire (CEBQ)., Results: The level of orexin was significantly decreased (P < 0.05), while ghrelin was significantly enhanced (P < 0.05) after 6 weeks. The scores of food responsiveness (FR) and enjoyment of food (EF) of the CEBQ were significantly decreased (P < 0.05) after intervention. The changes of leptin and that of SR were significantly correlated (r = - 0.455, P < 0.05), and the correlation between the alterations of orexin and that of EF was moderate with significance (r = 0.625, P < 0.05). miR-103a-3p expression was not statistically changed, while miR-200a-3p was significantly inhibited after 6-week intervention (P < 0.05). The correlation between relative changes of miR-103a-3p and that of leptin and orexin were both with significant difference (r = 0.413, P < 0.05; r = 0.409, P < 0.05), whereas the alterations of miR-200a-3p were not correlative with hormones or appetite sensation., Conclusion: Exercise combined with diet intervention for 6 weeks was effective in regulating appetite sensations and hormones in obese children, and miR-103a-3p and miR-200a-3p might provide a foundation for target biomarkers of appetite trait in modulating the energy balance control by exercise and dietary intervention., Level of Evidence: Level III, case-control analytic study., Trial Registration: The trial was registered in ClinicalTrials.gov (NCT03762629).

Background: Myocardial infarction (MI) and heart failure remain critical states of heart disease with high mortality. Previous studies have indicated that miRNA has cardioprotective effects and can resist myocardial ischemia-reperfusion (I/R) injury. However, the role of mir-384-3p in MI has not been reported, and whether this miRNA can regulate the apoptosis of cardiomyocytes needs to be verified., Methods: The effect of hypoxia-reperfusion (H/R) on cardiomyocyte activity was detected using MTT assay. MiR-384-3p was knocked down or overexpressed in cardiomyocytes H/R models by pretreatment with miR-384-3p mimic or inhibitor to verify the function of miR-384-3p in H/R. Circulating levels of miR-384-3p was detected by quantitative realtime PCR, and protein expression was detected by western blotting. TUNEL staining and flow cytometry demonstrated a high degree of myocardium apoptosis after H/R induction. Dual-Luciferase Reporter Assay detected dynamic expression of miR-384-3p and HSP70. The infarction size of I/R rats was detected by 2,3,5-triphenyltetrazolium chloride (TTC) staining., Results: MiR-384-3p was closely related to cardiomyocyte activity in H/R progression. Increased expression of mir-384-3p can promote the production of cleaved caspase-3 and cleaved PARP, thereby regulating cardiomyocyte apoptosis. HSP70 was a target of miR-384-3p and HSP70 silencing aggravated H/R-induced cardiomyocyte dysfunction. In an animal model, the expression level of HSP70 is regulated by miR-384-3p, and miR-384-3p inhibition remarkably reduced I/R-induced MI in rats., Conclusion: In conclusion, the present report identified that HSP70 was a potential target of miR-384-3p, and miR-384-3p inhibition remarkably reduced I/R-induced MI in rats. Therefore, this study provides a novel therapeutic approach for the treatment of MI from bench to clinic., (2021 Forum Multimedia Publishing, LLC)

An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in malignant tumor initiation and progression; however, many circRNAs are yet unidentified, and the role of circRNAs in nasopharyngeal carcinoma (NPC) is unclear. Using RNA sequencing, we discovered a novel circRNA, termed circARHGAP12, that was processed from the pre-mRNA of the ARHGAP12 gene. CircARHGAP12 was significantly upregulated in NPC tissues and cell lines and promoted NPC cell migration and invasion. Overexpression or knockdown experiments revealed that circARHGAP12 regulates the expression of cytoskeletal remodeling-related proteins EZR, TPM3, and RhoA. CircARHGAP12 was found to bind directly to the 3' UTR of EZR mRNA and promote its stability; moreover, EZR protein interacted with TPM3 and RhoA and formed a complex to promote NPC cell invasion and metastasis. This study identified the novel circRNA circARHGAP12, characterized its biological function and mechanism, and increased our understanding of circRNAs in NPC pathogenesis. In particular, circARHGAP12 was found to promote the malignant biological phenotype of NPC via cytoskeletal remodeling, thus providing a clue for targeted therapy of NPC., (Copyright © 2020 Elsevier B.V. All rights reserved.)