Long non-coding RNAs expression profile in HepG2 cells reveals the potential role of long non-coding RNAs in the cholesterol metabolism

Chin Med J (Engl). 2015 Jan 5;128(1):91-7. doi: 10.4103/0366-6999.147824.

Abstract

Background: Green tea has been shown to improve cholesterol metabolism in animal studies, but the molecular mechanisms underlying this function have not been fully understood. Long non-coding RNAs (lncRNAs) have recently emerged as a major class of regulatory molecules involved in a broad range of biological processes and complex diseases. Our aim was to identify important lncRNAs that might play an important role in contributing to the benefits of epigallocatechin-3-gallate (EGCG) on cholesterol metabolism.

Methods: Microarrays was used to reveal the lncRNA and mRNA profiles in green tea polyphenol(-)-epigallocatechin gallate in cultured human liver (HepG2) hepatocytes treated with EGCG and bioinformatic analyses of the predicted target genes were performed to identify lncRNA-mRNA targeting relationships. RNA interference was used to investigate the role of lncRNAs in cholesterol metabolism.

Results: The expression levels of 15 genes related to cholesterol metabolism and 285 lncRNAs were changed by EGCG treatment. Bioinformatic analysis found five matched lncRNA-mRNA pairs for five differentially expressed lncRNAs and four differentially expressed mRNA. In particular, the lncRNA AT102202 and its potential targets mRNA-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) were identified. Using a real-time polymerase chain reaction technique, we confirmed that EGCG down-regulated mRNA expression level of the HMGCR and up-regulated expression of AT102202. After AT102202 knockdown in HepG2, we observed that the level of HMGCR expression was significantly increased relative to the scrambled small interfering RNA control (P < 0.05).

Conclusions: Our results indicated that EGCG improved cholesterol metabolism and meanwhile changed the lncRNAs expression profile in HepG2 cells. LncRNAs may play an important role in the cholesterol metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catechin / analogs & derivatives
  • Catechin / metabolism
  • Cell Line, Tumor
  • Cholesterol / metabolism*
  • Hep G2 Cells
  • Humans
  • RNA, Long Noncoding / genetics*

Substances

  • RNA, Long Noncoding
  • Catechin
  • Cholesterol
  • epigallocatechin gallate