Long Non-coding RNA: An Emerging Contributor and Potential Therapeutic Target in Renal Fibrosis.
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ABSTRACT:
SUBMITTER: Xia W
PROVIDER: S-EPMC8353329 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Although long non-coding RNAs (lncRNAs) are important players in the initiation and progression of many pathological processes, the role of lncRNAs in renal fibrosis still remains unclear. We showed that lncRNA-H19 expression was significantly up-regulated in TGF-?2-induced HK-2 cell fibrosis and unilateral ureteral obstruction (UUO)-induced renal fibrosis in vivo. H19 knockdown significantly attenuated renal fibrosis in vitro and in vivo. LncRNA-H19, miR-17, and fibronectin constituted to a regulatory network involved in renal fibrosis. We also detected up-regulated H19 expression and down-regulated miR-17 expression in the early and advanced animal models of renal fibrosis. This study indicates that H19 up-regulation contributes to renal fibrosis. H19 inhibition might represent a novel anti-fibrotic treatment in renal diseases.
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Project description:Esophageal cancer (EC) is one type of aggressive gastrointestinal cancers. The treatment of EC is challenging. Effective therapeutic targets require development. Long non-coding RNA TRPM2 antisense RNA (LncRNA TRPM2-AS) is considering a novel biomarker and therapeutic target for various types of cancer. However, the role of lncRNA TRPM2-AS in EC remains unknown. This study aimed to illustrate effects of LncRNA TRPM2-AS on EC growth and metastasis and potential underlying molecular mechanisms. LncRNA TRPM2-AS expression was determined in both EC tissues and cell lines by quantitative real-time polymerase-chain reaction (qRT-PCR). Cell proliferation ability was evaluated by cell counting kit-8 and colony formation assays. Cell apoptosis was analyzed by flow cytometry. Cell migration and invasion were determined using transwell. Epithelial-mesenchymal transition (EMT)-related markers expression were determined using qRT-PCR and Western blotting. Furthermore, potential lncRNA TRPM2-AS targeting miRNAs were predicted by public databases. The expression of five selected miRNAs were validated by qRT-PCR. We found that lncRNA TRPM2-AS expression was increased in EC tissues and cell lines compared with respective control. Silencing lncRNA TRPM2-AS suppressed EC cell proliferation, migration, and invasion while promoted cell apoptosis. Moreover, lncRNA TRPM2-AS knockdown reduced neural cadherin, vimentin, and matrix metallopeptidase 9 gene and protein expressions while increased epithelial cadherin expression. Furthermore, lncRNA TRPM2-AS knockdown promoted microRNA (miR)-1291, miR-6852-5p, and miR-138-5p expressions. Taken together, this study for the first time demonstrates that upregulation of lncRNA TRPM2-AS in EC promotes the growth and metastasis of EC likely through interacting with miR-1291, miR-6852-5p, and miR-138-5p.
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Project description:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality, which threats peoples' health. Unfortunately, the pathogenesis of PDAC remains unclear. Recent studies have indicated that long non-coding RNAs (lncRNAs) can regulate the development and progression of malignant tumors through varying mechanisms. LncRNA H19 has a unique expression profile and can act as a sponger of specific miRNAs to regulate the pathogenic process of many diseases, including PDAC and several other types of cancers. Here, we review the research approaches to understanding the regulatory role of H19 and potential mechanisms in the progression of PDAC and other types of cancers and diseases. These studies suggest that H19 may be a novel therapeutic target for PDAC and our findings may open new revenues for scientific researches and development of valuable therapies for these diseases in the future.
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Project description:Many studies have made clear that most of the genome is transcribed into noncoding RNAs, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), both of which can affect different cell features. LncRNAs are long heterogeneous RNAs that regulate gene expression and a variety of signaling pathways involved in cellular homeostasis and development. Several studies have demonstrated that lncRNA is an important class of regulatory molecule that can be targeted to change cellular physiology and function. The expression or dysfunction of lncRNAs is closely related to various hereditary, autoimmune, and metabolic diseases, and tumors. Specifically, recent work has shown that lncRNAs have an important role in kidney pathogenesis. The effective roles of lncRNAs have been recognized in renal ischemia, injury, inflammation, fibrosis, glomerular diseases, renal transplantation, and renal-cell carcinoma. The present review focuses on the emerging role and function of lncRNAs in the pathogenesis of kidney inflammation and fibrosis as novel essential regulators. Although lncRNAs are important players in the initiation and progression of many pathological processes, their role in renal fibrosis remains unclear. This review summarizes the current understanding of lncRNAs in the pathogenesis of kidney fibrosis and elucidates the potential role of these novel regulatory molecules as therapeutic targets for the clinical treatment of kidney inflammation and fibrosis.
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Project description:IntroductionNeutrophil extracellular traps (NETs) are web-like structures composed of nuclear and granular components. The primary role of NETS is to prevent the dissemination of microbes and facilitate their elimination. However, this process is accompanied by collateral proinflammatory adverse effects when the NET release becomes uncontrollable, or clearance is impaired. Although NET-induced organ damage is conducted primarily and indirectly via immune complexes and the subsequent release of cytokines, their direct effects on cells are also remarkable. NETosis plays a critical pathogenic role in several renal disorders, such as the early phase of acute tubular necrosis, anti-neutrophil cytoplasmic antibody-mediated renal vasculitis, lupus nephritis, thrombotic microangiopathies, anti-glomerular basement membrane disease, and diabetic nephropathy. Their substantial contribution in the course of these disorders makes them a desirable target in the therapeutic armamentarium. This article gives an in-depth review of the heterogeneous pathogenesis and physiological regulations of NETosis and its pivotal role in renal diseases. Based on the pathogenesis, the article also outlines the current therapeutic options and possible molecular targets in the treatment of NET-related renal disorders.MethodsWe carried out thorough literature research published in PubMed and Google Scholar, including a comprehensive review and analysis of the classification, pathomechanisms, and a broad spectrum of NET-related kidney disorders.ConclusionsNETosis plays a pivotal role in certain renal diseases. It initiates and maintains inflammatory and autoimmune disorders, thus making it a desirable target for improving patient and renal outcomes. Better understanding and clinical translation of the pathogenesis are crucial aspects to treatment, for improving patient, and renal outcomes.
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Project description:Renal fibrosis is one of the most characterized pathological features in chronic kidney disease (CKD). Progressive fibrosis eventually leads to renal failure, leaving dialysis or allograft transplantation the only clinical option for CKD patients. Transforming growth factor-β (TGF-β) is the key mediator in renal fibrosis and is an essential regulator for renal inflammation. Therefore, the general blockade of the pro-fibrotic TGF-β may reduce fibrosis but may risk promoting renal inflammation and other side effects due to the diverse role of TGF-β in kidney diseases. Long non-coding RNAs (lncRNAs) are RNA transcripts with more than 200 nucleotides and have been regarded as promising therapeutic targets for many diseases. This review focuses on the importance of TGF-β and lncRNAs in renal inflammation, fibrogenesis, and the potential applications of TGF-β and lncRNAs as the therapeutic targets and biomarkers in renal fibrosis and CKD are highlighted.
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