Long Non-Coding RNA Small Nucleolar RNA Host Gene 1 Alleviates Sepsis-Associated Myocardial Injury by Modulating the miR-181a-5p/XIAP Axis in vitro

Ann Clin Lab Sci. 2021 Mar;51(2):231-240.

Abstract

Objective: Sepsis is a systemic inflammatory response syndrome that results in severe myocardial injury. This study aimed to explore the role and mechanism of long non-coding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in sepsis-induced myocardial injury in vitro.

Methods: Embryonic rat ventricular myocardial cell line (H9c2) was treated with lipopolysaccharide (LPS) to simulate sepsis-induced myocardial injury in vitro. A quantitative real-time polymerase chain reaction was executed to determine the expression of SNHG1 and microRNA (miR)-181a-5p. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay was employed to measure cell viability. The levels of inflammatory factors (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], and IL-1β) were measured by enzyme-linked immunosorbent assay. Oxidative stress was assessed by measuring malondialdehyde, superoxide dismutase, and lactate dehydrogenase. The targeted interrelations among SNHG1, miR-181a-5p, and X-linked inhibitor of apoptosis protein (XIAP) were verified by dual-luciferase reporter assay. Relative protein expression of XIAP was detected by western blot.

Results: SNHG1 and XIAP were down-regulated, and miR-181a-5p was up-regulated in LPS-induced H9c2 cells. Overexpression of SNHG1 or inhibition of miR-181a-5p facilitated cell viability and repressed inflammation and oxidative stress in LPS-treated H9c2 cells. MiR-181a-5p was a target of and negatively regulated by SNHG1. At the same time, XIAP was a target gene of and inversely modulated by miR-181a-5p. In addition, XIAP was positively regulated by SNHG1. Up-regulation of miR-181a-5p or silencing of XIAP reversed the inhibitory effects of SNHG1 on inflammation and oxidative stress, as well as the promoting effects on cell viability in LPS-induced H9c2 cells.

Conclusion: SNHG1 protected H9c2 cells against LPS-induced injury through modulating the miR-181a-5p/XIAP axis.

Keywords: SNHG1; XIAP; miR-181a-5p; myocardial injury; sepsis.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Heart Injuries / genetics*
  • Heart Injuries / metabolism
  • Humans
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • MicroRNAs / genetics
  • Myocardium / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Nucleolar / pharmacology
  • Rats
  • Sepsis / complications
  • Sepsis / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • X-Linked Inhibitor of Apoptosis Protein / genetics

Substances

  • Interleukin-1beta
  • Interleukin-6
  • MIRN181 microRNA, rat
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Nucleolar
  • Tumor Necrosis Factor-alpha
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • long non-coding RNA SNHG1, human