A novel long noncoding RNA Lnc-HC binds hnRNPA2B1 to regulate expressions of Cyp7a1 and Abca1 in hepatocytic cholesterol metabolism

Hepatology. 2016 Jul;64(1):58-72. doi: 10.1002/hep.28391. Epub 2016 Jan 22.

Abstract

Cholesterol metabolism disorder in hepatocytes predicts a higher risk of metabolic syndrome (MetS). Long noncoding RNAs (lncRNAs) have emerged as critical players in cellular cholesterol metabolism, but their functions are not systematically clarified. Here, we have identified a novel lncRNA named lnc-HC negatively regulating cholesterol metabolism within hepatocytes through physical interaction with hnRNPA2B1. By further binding to the target messenger RNA of Cyp7a1 or Abca1, the lnc-HC-hnRNPA2B1 complex decreases expressions of the two genes that are implicated in cellular cholesterol excretion. lnc-HC knockdown can strongly recover the cholesterol disorder in vivo. In the upstream pathway, lnc-HC is up-regulated by high cholesterol by the transcription activator, CCAAT/enhancer-binding protein beta.

Conclusion: These findings suggest a subtle feed-forward regulation of lnc-HC in cholesterol metabolism and define a novel line of evidence by which lncRNAs modulate the metabolic system at the post-transcriptional level. (Hepatology 2016;64:58-72).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism*
  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / metabolism
  • Cholesterol / metabolism*
  • Cholesterol 7-alpha-Hydroxylase / metabolism*
  • Gene Expression Regulation
  • Hepatocytes / enzymology*
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B / metabolism*
  • Humans
  • Liver / metabolism
  • Mice
  • RNA, Long Noncoding / metabolism*
  • Random Allocation
  • Rats

Substances

  • ABCA1 protein, rat
  • ATP Binding Cassette Transporter 1
  • CCAAT-Enhancer-Binding Protein-beta
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • RNA, Long Noncoding
  • long noncoding RNA Lnc-HC, rat
  • Cholesterol
  • CYP7A1 protein, rat
  • Cholesterol 7-alpha-Hydroxylase