1. Academic Validation
  2. LncRNA SNHG15 Modulates Ischemia-Reperfusion Injury in Human AC16 Cardiomyocytes Depending on the Regulation of the miR-335-3p/TLR4/NF-κB Pathway

LncRNA SNHG15 Modulates Ischemia-Reperfusion Injury in Human AC16 Cardiomyocytes Depending on the Regulation of the miR-335-3p/TLR4/NF-κB Pathway

  • Int Heart J. 2022;63(3):578-590. doi: 10.1536/ihj.21-511.
Haibo Du 1 Lianqin Ding 2 Tian Zeng 3 Di Li 4 Li Liu 3
Affiliations

Affiliations

  • 1 Heart Disease Center, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine.
  • 2 Department of Cardiology, Shenzhen Samii Medical Center (The Fourth People's Hospital of Shenzhen).
  • 3 Department of Cardiology, Yibin Second People's Hospital.
  • 4 Department of Cardiology, Daqing Oil Field General Hospital.
Abstract

Myocardial ischemia-reperfusion (I/R) injury is a serious complication of acute myocardial infarction. Long noncoding RNA (lncRNA) small nucleolar RNA host gene 15 (SNHG15) can regulate I/R-induced cardiomyocyte Apoptosis. Here, we investigated the mechanism of SNHG15 activity in I/R-induced cardiomyocyte injury.SNHG15, MicroRNA (miR)-335-3p, and Toll-like Receptor 4 (TLR4) were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Cell viability, proliferation, and Apoptosis were gauged by Cell Counting Kit-8 (CCK-8) assay, 5-ethynyl-2´-deoxyuridine (EDU) assay, and flow cytometry, respectively. The direct relationship between miR-335-3p and SNHG15 or TLR4 was validated by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays.SNHG15 was overexpressed in the infarcted area tissues of I/R mice and I/R-stimulated AC16 cells. SNHG15 knockdown alleviated I/R injury in AC16 cells. Mechanistically, SNHG15 directly targeted miR-335-3p, and miR-335-3p was a functional mediator of SNHG15. MiR-335-3p inhibited TLR4 expression by targeting TLR4, and miR-335-3p-mediated inhibition of TLR4 alleviated I/R-induced injury in AC16 cells. Moreover, SNHG15 regulated the TLR4/nuclear factor-κB (NF-κB) signaling pathway through miR-335-3p.Our findings identify a novel mechanism, the miR-335-3p/TLR4/NF-κB pathway, for the regulation of SNHG15 in myocardial I/R injury.

Keywords

Acute myocardial infarction; Mechanism; Myocardial I/R injury.

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