例如:"lncRNA", "apoptosis", "WRKY"

miRNA-411 Regulates Chondrocyte Autophagy in Osteoarthritis by Targeting Hypoxia-Inducible Factor 1 alpha (HIF-1α).

Med Sci Monit. 2020 Feb 19;26:e921155
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摘要


BACKGROUND Osteoarthritis (OA) is the most common joint disease and is characterized by the progressive degeneration of articular cartilage. The molecular basis of OA involves various factors and has not been fully clarified. Autophagy is a conserved catabolic process that involves cellular degradation through the lysosomal machinery. MATERIAL AND METHODS We found that miRNA-411 regulates chondrocyte autophagy in OA by targeting hypoxia-inducible factor 1 alpha (HIF-1alpha) and identified the related molecular mechanism. OA condition in chondrocyte C28/I2 cells was induced by treatment with interleukin 1 beta (IL-1ß). The protein expressions of LC3, p62, HIF-1alpha, ULK-1, and Beclin-1 were assessed by Western blot analysis, and LC3 expression was assessed by immunofluorescence. RESULTS TargetScan analysis showed that HIF-1alpha mRNA is directly targeted by miR-411, which was confirmed by luciferase reporter assay. miR-411 mimic decreased HIF-1alpha levels in chondrocytes while miR-411 inhibitor increased HIF-1alpha levels in chondrocytes. Furthermore, expression of LC3, ULK-1, P62, and Beclin-1 in chondrocytes was induced by miR-411 inhibitor and was downregulated by miR-411 mimics. In addition, miR-411 mimics reduced the expression level of LC3, as determined by immunofluorescence analysis. CONCLUSIONS Our results demonstrate that miR-411 promotes chondrocyte autophagy by targeting HIF-1alpha, suggesting that regulating HIF-1alpha by miR-411 might be a therapeutic strategy for OA.

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