Diabetic Cardiomyopathy

MALAT1[LncRNA]

miR-141-3p[miRNA]

H9C2[mRNA]

H9C2 cells

Homo sapiens (human)

Mol Med Rep. 2021 Apr;23(4):259. doi: 10.3892/mmr.2021.11898. Epub 2021 Feb 12.

lncRNA-MALAT1 promotes high glucose-induced H9C2 cardiomyocyte pyroptosis by downregulating miR-141-3p expression.

qPCR;RT-qPCR;Western blot;

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.