LncRNA MEG3 aggravates palmitate-induced insulin resistance by regulating miR-185-5p/Egr2 axis in hepatic cells

Eur Rev Med Pharmacol Sci. 2019 Jun;23(12):5456-5467. doi: 10.26355/eurrev_201906_18215.

Abstract

Objective: Long non-coding RNA (LncRNA) has been reported to play an important role in type 2 diabetes (T2D). We investigated the role of LncRNA maternally expressed gene 3 (MEG3) and its potential interaction with miR-185-5p in palmitate-induced hepatocyte insulin resistance.

Patients and methods: High-fat diet (HFD) mice and insulin resistant hepatocyte were employed. Relative mRNA expressions of MEG3, miR-185-5p, and early growth response proteins-2 (Egr2) were measured by qRT-PCR. Western blot was performed to evaluate Egr2 protein expression levels. Glycogen contents and plasma insulin levels were tested by the corresponding assay.

Results: MEG3 and Egr2 were upregulated, but miR-185-5p was downregulated in palmitate-treated insulin resistance hepatocytes and HFD mice. MEG3 knockdown alleviated the influence of palmitate on insulin resistance in vitro and in vivo. miR-185-5p expression was upregulated upon MEG3 knockdown. Expression of Egr2 was positively correlated with MEG3 knockdown or overexpression, which could be negatively managed by abnormal expression of miR-185-5p.

Conclusions: Our data demonstrated that LncRNA MEG3 aggravated palmitate-induced insulin resistance by regulating miR-185-5p/Egr2 axis, providing new insights into T2D therapeutic strategies.

MeSH terms

  • Animals
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Early Growth Response Protein 2 / genetics*
  • Gene Knockdown Techniques
  • Hep G2 Cells
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism*
  • Humans
  • Insulin / metabolism
  • Insulin Resistance / genetics*
  • Male
  • Mice
  • MicroRNAs / metabolism*
  • Palmitates / toxicity
  • Primary Cell Culture
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation / drug effects

Substances

  • EGR2 protein, human
  • Early Growth Response Protein 2
  • Egr2 protein, mouse
  • Insulin
  • MEG3 non-coding RNA, human
  • MEG3 non-coding RNA, mouse
  • MIRN185 microRNA, human
  • MicroRNAs
  • Mirn185 microRNA, mouse
  • Palmitates
  • RNA, Long Noncoding