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.

• PMID: 37006883
• PMCID: PMC10061048
• DOI: 10.3892/etm.2023.11879

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.