Dataset Information

CircRNF111 Protects Against Insulin Resistance and Lipid Deposition via Regulating miR-143-3p/IGF2R Axis in Metabolic Syndrome.

ABSTRACT: Abnormal expression of circRNAs (circular RNAs), a subclass of non-coding RNAs, has been documented in numerous human diseases. Herein, we explored whether circRNAs act as ceRNAs (competing endogenous RNAs) to modulate the pathological process-insulin resistance, as well as dyslipidemia of MetS (Metabolic Syndrome). The profile of circRNAs in serume of MetS and control samples was characterized by circRNA deep sequencing. We identified circRNF111 as a key downregulated circRNA involved in MetS. The decreased expression of circRNF111 in the serum samples of MetS was directly linked to excessive insulin resistance and dyslipidemia. Loss-of-function experiments showed that circRNF111 knockdown inhibited the glucose uptake and the Akt signaling pathway, meanwhile increased the deposition of triglycerides in adipogenic differentiated hADSCs (human adipose-derived stem cells). Mechanistically, circRNF111 sponged miR-143-3p and functioned via targeting miR-143-3p along with its downstream target gene IGF2R. The role along with the mechanism of circRNF111 sponging miR-143-3p in MetS was also explored in obese mice triggered by high-fat die. Therefore, our data suggest a protective role of the novel circRNA-circRNF111 in MetS progression. CircRNF111 inhibition enhances insulin resistance and lipid deposition in MetS through regulating miR-143-3p-IGF2R cascade. This provides a promising therapeutic approach for MetS.

SUBMITTER: Lin X

PROVIDER: S-EPMC8415985 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CircRNF111 Protects Against Insulin Resistance and Lipid Deposition via Regulating miR-143-3p/IGF2R Axis in Metabolic Syndrome.

Lin Xihua X Du Ying Y Lu Weina W Gui Weiwei W Sun Shuiya S Zhu Yiyi Y Wang Gangliang G Eserberg Daniel Turunen DT Zheng Fenping F Zhou Jiaqiang J Wu Fang F Li Hong H

Frontiers in cell and developmental biology 20210817

Abnormal expression of circRNAs (circular RNAs), a subclass of non-coding RNAs, has been documented in numerous human diseases. Herein, we explored whether circRNAs act as ceRNAs (competing endogenous RNAs) to modulate the pathological process-insulin resistance, as well as dyslipidemia of MetS (Metabolic Syndrome). The profile of circRNAs in serume of MetS and control samples was characterized by circRNA deep sequencing. We identified circRNF111 as a key downregulated circRNA involved in MetS. ...[more]

PMID: 34485272

Similar Datasets

Project description:BackgroundSenescent adipose-derived stem cells (ASCs) exhibit reduced therapeutic efficacy during wound healing. Transcriptional regulation factors including long noncoding RNAs (lncRNAs) reportedly have essential roles in stem cell aging. However, the mechanisms of which lncRNAs influence mesenchymal stem cell aging and how it works need further investigation.MethodsThe expression patterns of lncRNA senescence-associated noncoding RNA (SAN) and miR-143-3p in ASCs obtained from old and young volunteer donors were detected by quantitative polymerase chain reaction. ASCs with overexpression or knockdown of SAN and γ-adducin (ADD3) were constructed by lentiviral transduction. Mimic and inhibitor were used to manipulate the cellular level of miR-143-3p in ASCs. The effects of these RNAs on ASCs proliferation, migration and cellular senescence were examined by EdU, transwell and senescence-activated β-galactosidase (SA-β-gal) staining assays. Wound scratch and tube formation assays were conducted to evaluate the capacities of ASCs in promoting fibroblasts migration and endothelial cells angiogenesis. Furthermore, dual-luciferase assays and rescue experiments were performed to identify the RNA interactions. Finally, the therapeutic effects of SAN-depleted aged ASCs were evaluated in a skin injury model.ResultsThe lncRNA SAN (NONHSAT035482.2) was upregulated in aged ASCs; it controlled cellular senescence in ASCs. lncRNA SAN knockdown in ASCs led to ASC functional enhancement and the inhibition of cellular senescence; it also promoted the effects of conditioned medium (CM) on endothelial cell tube formation and fibroblast migration. Mechanistic analysis showed that SAN serves as a sponge for miR-143-3p, thereby regulating the expression of ADD3. The application of SAN-depleted aged ASCs increased re-epithelialization, collagen deposition, neovascularization and led to accelerated skin wound closure, compared with transplantation of aged ASCs.ConclusionThe lncRNA SAN mediates ASC senescence by regulating the miR-143-3p/ADD3 pathway, providing a potential target for rejuvenation of senescent ASCs and enhancement of wound repair.

Project description:Few studies have addressed the mechanism by which circ_0010729 regulates hypoxia-induced cell injury in cardiovascular diseases. However, its role and its regulatory mechanism in myocardial infarction remain to be explored. Cell viability, cycle, apoptosis, and migration were analyzed using cell counting kit-8 assay, flow cytometry, caspase-3 activity assay kit and transwell assay, respectively. Tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentrations were examined by enzyme-linked immunosorbent assay. Glucose metabolism was calculated by detecting ATP production, glucose uptake and lactate production. Levels of circ_0010729, miR-370-3p and TNF Receptor Associated Factor 6 (TRAF6) were detected using quantitative real-time polymerase chain reaction or western blot. The direct interaction between circ_0010729 and TRAF6 or miR-370-3p was verified using dual-luciferase reporter assay and RNA immunoprecipitation assay. Under hypoxia condition, cardiomyocytes suffered from cell viability suppression, cell cycle arrest, cell apoptosis promotion, migration reduction, increase of inflammatory factor IL-6 and TNF-α, as well as glycolysis inhibition. Circ_0010729 expression was up-regulated in the cardiomyocytes at different hypoxia-exposed time points. Circ_0010729 knockdown protected cardiomyocytes against hypoxic dysfunction, while circ_0010729 overexpression showed inverse effects. MiR-370-3p was confirmed to directly bind to circ_0010729 or TRAF6. MiR-370-3p inhibition attenuated the protective effects of circ_0010729 knockdown on hypoxia-modulated cardiomyocyte dysfunction. MiR-370-3p restoration protected cardiomyocytes against hypoxic injury via targeting TRAF6. Besides, circ_0010729 indirectly regulated TRAF6 expression via miR-370-3p. This study demonstrated that circ_0010729 knockdown attenuated hypoxia-induced cardiomyocyte dysfunction via miR-370-3p/TRAF6 axis, indicating a potential therapeutic target for myocardial infarction.

Dataset Information

CircRNF111 Protects Against Insulin Resistance and Lipid Deposition via Regulating miR-143-3p/IGF2R Axis in Metabolic Syndrome.

Publications

CircRNF111 Protects Against Insulin Resistance and Lipid Deposition via Regulating miR-143-3p/IGF2R Axis in Metabolic Syndrome.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets