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  • Title: lncRNA‑MALAT1 promotes high glucose‑induced H9C2 cardiomyocyte pyroptosis by downregulating miR‑141‑3p expression.
    Author: Wu A, Sun W, Mou F.
    Journal: Mol Med Rep; 2021 Apr; 23(4):. PubMed ID: 33576445.
    Abstract:
    Diabetic cardiomyopathy (DCM) is caused by diabetes and can result in heart failure. Long non‑coding RNAs (lncRNAs) have been demonstrated to be closely associated with DCM development. The present study aimed to investigate whether lncRNA‑metastasis‑associated lung adenocarcinoma transcript‑1 (MALAT1) altered high glucose (HG)‑induced H9C2 cardiomyocyte pyroptosis by targeting microRNA (miR)‑141‑3p. H9C2 cells were treated with normal glucose (NG) or HG. lncRNA‑MALAT1 and miR‑141‑3p expression levels were determined via reverse transcription‑quantitative PCR (RT‑qPCR). MALAT1 and miR‑141‑3p knockdown and overexpression were established and confirmed via RT‑qPCR. The association between MALAT1 expression and miR‑141‑3p expression, as well as the induction of pyroptosis and gasdermin D (GSDMD)‑N expression were evaluated by performing dual luciferase reporter, TUNEL staining and immunofluorescence staining assays, respectively. Western blotting was conducted to measure the expression levels of pyroptosis‑associated proteins, including apoptosis‑associated speck‑like protein, GSDMD‑N, caspase‑1, nucleotide oligomerization domain‑like receptor protein 3 and GSDMD. MALAT1 mRNA expression levels were significantly increased, whereas miR‑141‑3p expression levels were significantly decreased in HG‑treated H9C2 cells compared with the NG group. Compared with the HG group, MALAT1 overexpression significantly reduced miR‑141‑3p expression levels, increased the rate of TUNEL positive cells and upregulated the expression levels of pyroptosis‑associated proteins. MALAT1 knockdown displayed the opposite effect on the rate of TUNEL positive cells and the expression levels of pyroptosis‑associated proteins. Furthermore, the rate of TUNEL positive cells, and GSDMD‑N and pyroptosis‑associated protein expression levels were significantly reduced by miR‑141‑3p overexpression in MALAT1‑overexpression H9C2 cells. The results indicated that compared with NG treatment, HG treatment increased MALAT1 expression levels and decreased miR‑141‑3p expression levels in H9C2 cells. Therefore, the present study suggested that lncRNA‑MALAT1 targeted miR‑141‑3p to promote HG‑induced H9C2 cardiomyocyte pyroptosis.
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