Exp Ther Med. 2023 Mar 10;25(4):180.doi: 10.3892/etm.2023.11879. eCollection 2023 Apr.

本文采用的英格恩产品: RNA-Entranster-invivo

miR‑30c reduces myocardial ischemia/reperfusion injury by targeting SOX9 and suppressing pyroptosis

Jia Nie  1 Wenjing Zhou  1   2 Shouyang Yu  2 Song Cao  1   2 Haiying Wang  1   2 Tian Yu  2

Affiliations

Affiliations

  • 1 Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.
  • 2 Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.

Free PMC article

Abstract

MicroRNAs (miRNAs or miRs) are commonly involved in regulating myocardial ischemia/reperfusion (I/R) injury by binding and silencing their target genes. However, whether miRNAs regulate myocardial I/R-induced pyroptosis remains unclear. The present study established an in vivo rat model of myocardial I/R injury and in vitro hypoxia/reoxygenation (H/R) injury model in rat primary cardiomyocytes to investigate the function and the underlying mechanisms of miRNAs on I/R injury-induced pyroptosis. RNA sequencing was utilized to select the candidate miRNAs between normal and I/R group. Reverse transcription-quantitative PCR and western blotting were performed to detect candidate miRNAs (miR-30c-5p, also known as miR-30c) and SRY-related high mobility group-box gene 9 (SOX9) expression, as well as expression of pyroptosis-associated proteins (NF-κB, ASC, caspase-1, NLRP3) in the myocardial I/R model. ELISA was used to measure pyroptosis-associated inflammatory markers IL-18 and IL-1β. Moreover, the link between miR-30c and SOX9 was predicted using bioinformatics and luciferase reporter assay. In myocardial I/R injured rats, miR-30c was downregulated, while the expression of SOX9 was upregulated. Overexpression of miR-30c inhibited pyroptosis both in vivo and in vitro. Furthermore, miR-30c negatively regulated SOX9 expression by binding its 3’untranslated region. In conclusion, the miR-30c/SOX9 axis decreased myocardial I/R injury by suppressing pyroptosis, which may be a potential therapeutic target.

Keywords: SRY-related high mobility group-Box gene 9; microRNA-30c; myocardial ischemia/reperfusion injury; pyroptosis.

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