Mechanisms by Which Silencing Long-stranded Noncoding RNA KCNQ1OT1 Alleviates Myocardial Ischemia/reperfusion Injury (MI/RI)-induced Cardiac Injury Via MiR-377-3p/HMOX1

Overview

Journal BMC Cardiovasc Disord

Publisher Biomed Central

Specialty Cardiology & Vascular Diseases

Date 2024 Jan 3

PMID 38172743

Authors

Tongcai Tan

Liang Tu

Yanmei Yu

Minjie He

Xingchao Zhou

Lei Yang

Affiliations

Soon will be listed here.

Abstract

Background: The key complication of myocardial infarction therapy is myocardial ischemia/reperfusion injury (MI/RI), and there is no effective treatment. The present study elucidates the mechanism of action of lncRNA KCNQ1OT1 in alleviating MI/RI and provides new perspectives and therapeutic targets for cardiac injury-related diseases.

Methods: An ischemia/reperfusion (I/R) injury model of human adult cardiac myocytes (HACMs) was constructed, and the expression of KCNQ1OT1 and miR-377-3p was determined by RT‒qPCR. The levels of related proteins were detected by western blot analysis. Cell proliferation was detected by a CCK-8 assay, and cell apoptosis and ROS content were determined by flow cytometry. SOD and MDA expression as well as Fe changes were detected by related analysis kits. The target binding relationships between lncRNA KCNQ1OT1 and miR-377-3p as well as between miR-377-3p and heme oxygenase 1 (HMOX1) were verified by a dual-luciferase reporter gene assay.

Results: Myocardial ischemia‒reperfusion caused oxidative stress in HACMs, resulting in elevated ROS levels, increased Fe levels, decreased cell viability, and increased LDH release (a marker of myocardial injury), and apoptosis. KCNQ1OT1 and HMOX1 were upregulated in I/R-induced myocardial injury, but the level of miR-377-3p was decreased. A dual-luciferase reporter gene assay indicated that lncRNA KCNQ1OT1 targets miR-377-3p and that miR-377-3p targets HMOX1. Inhibition of HMOX1 alleviated miR-377-3p downregulation-induced myocardial injury. Furthermore, lncRNA KCNQ1OT1 promoted the level of HMOX1 by binding to miR-377-3p and aggravated myocardial injury.

Conclusion: LncRNA KCNQ1OT1 aggravates ischemia‒reperfusion-induced cardiac injury via miR-377-3P/HMOX1.

Citing Articles

Epigenetic regulation and post-translational modifications of ferroptosis-related factors in cardiovascular diseases.

Jing C, Wu Y, Zhang Y, Zhu Z, Zhang Y, Liu Z Clin Epigenetics. 2025; 17(1):4.

PMID: 39799367 PMC: 11724467. DOI: 10.1186/s13148-024-01809-5.

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