LncRNA myocardial infarction-associated transcript (MIAT) contributed to cardiac hypertrophy by regulating TLR4 via miR-93

Eur J Pharmacol. 2018 Jan 5:818:508-517. doi: 10.1016/j.ejphar.2017.11.031. Epub 2017 Nov 21.

Abstract

It has been reported that lncRNA myocardial infarction-associated transcript (MIAT) facilitated the pathological development in angiotensin II (AngII)-induced cardiac hypertrophy. Nevertheless, the underlying mechanism of MIAT involved in cardiac hypertrophy is largely unknown. In this study, AngII-treated cardiomyocytes were applied as a cardiac hypertrophy model in vitro. The expressions of MIAT and miR-93 were detected by qRT-PCR. The protein levels of toll-like receptor 4 (TLR4), atrial natriuretic factor (ANF), beta-myosin heavy chain (β-MHC), phosphoinositide-3 kinase (PI3K), protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), and phosphorylated mTOR (p-mTOR) were determined by western blot. Luciferase reporter assay and RNA immunoprecipitation (RIP) were performed to explore the relationship between MIAT, TLR4 and miR-93. Hypertrophic response was assessed by measuring cell surface area and quantifying the expressions of ANF and β-MHC. The results demonstrated that MIAT was upregulated and miR-93 was downregulated in AngII-treated cardiomyocytes. MIAT functioned as a molecular sponge of miR-93 in cardiomyocytes. Additionally, TLR4 was identified as a target of miR-93 and MIAT promoted TLR4 expression by sponging miR-93. MIAT knockdown decreased cell surface area and the expression levels of ANF and β-MHC in AngII-treated cardiomyocytes by modulating miR-93. Moreover, enforced expression of TLR4 partially reversed the protective effect of miR-93 overexpression on AngII-induced cardiac hypertrophy. Furthermore, MIAT knockdown or miR-93 overexpression inactivated the PI3K/Akt/mTOR pathway via TLR4 in AngII-induced cardiac hypertrophy. Taken together, these data suggested that MIAT knockdown inhibited AngII-induced cardiac hypertrophy by regulating miR-93/TLR4 axis, highlighting a promising therapy target for cardiac hypertrophy.

Keywords: AngII; Cardiac hypertrophy; LncRNA; MIAT; MiR-93; TLR4.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Base Sequence
  • Cardiomegaly / genetics*
  • Cardiomegaly / metabolism*
  • Cardiomegaly / pathology
  • Gene Knockdown Techniques
  • MicroRNAs / genetics*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / genetics*
  • Rats
  • Rats, Wistar
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 4 / metabolism*
  • Up-Regulation / genetics

Substances

  • Miat long non-coding RNA
  • MicroRNAs
  • Mirn93 microRNA, rat
  • RNA, Long Noncoding
  • Toll-Like Receptor 4
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases