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  • Title: Circ_WBSCR17 aggravates inflammatory responses and fibrosis by targeting miR-185-5p/SOX6 regulatory axis in high glucose-induced human kidney tubular cells.
    Author: Li G, Qin Y, Qin S, Zhou X, Zhao W, Zhang D.
    Journal: Life Sci; 2020 Oct 15; 259():118269. PubMed ID: 32798559.
    Abstract:
    BACKGROUND: Diabetic nephropathy (DN), a severe microvascular complication of diabetes, has complex pathogenesis. Circular RNAs (circRNAs) exert broad biological functions on human diseases. This study intended to explore the role and mechanism of circ_WBSCR17 in DN. METHODS: DN mice models were constructed using streptozotocin injection, and DN cell models were assembled using high glucose (HG) treatment in human kidney 2 cells (HK-2). The expression of circ_WBSCR17, miR-185-5p and SRY-Box Transcription Factor 6 (SOX6) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of SOX6 and fibrosis markers were examined by western blot. The release of inflammatory cytokines, cell proliferation and apoptosis, were assessed by enzyme-linked immunosorbent assay (ELISA), cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The predicted interaction between miR-185-5p and circ_WBSCR17 or SOX6 was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULT: Circ_WBSCR17 was highly expressed in DN mice models and HG-induced HK-2 cells. Circ_WBSCR17 knockdown or SOX6 knockdown promoted cell proliferation and blocked cell apoptosis, inflammatory responses and fibrosis, while circ_WBSCR17 overexpression or SOX6 overexpression conveyed the opposite effects. MiR-185-5p was a target of circ_WBSCR17 and directly bound to SOX6. MiR-185-5p could reverse the role of circ_WBSCR17 or SOX6. Moreover, the expression of SOX6 was modulated by circ_WBSCR17 through intermediating miR-185-5p. CONCLUSION: Circ_WBSCR17 triggered the dysfunction of HG-induced HK-2 cells, including inflammatory responses and fibrosis, which was accomplished via the miR-185-5p/SOX6 regulatory axis.
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