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Long noncoding RNA CCAT1 inhibits miR-613 to promote nonalcoholic fatty liver disease via increasing LXRα

Feizhou Huang1, Huaizheng Liu1, Zhao Lei1

  • 1Emergency Department, The Third Xiangya Hospital, Central South University, Changsha, China.

Journal of Cellular Physiology
|May 16, 2020
PubMed

Insights

CCAT1, a long noncoding RNA, promotes lipid droplet formation in nonalcoholic fatty liver disease (NAFLD) by upregulating LXRα. Targeting CCAT1 and LXRα may offer new treatments for NAFLD.

Area of Science:

  • Molecular Biology
  • Hepatology
  • Genetics

Background:

  • Nonalcoholic fatty liver disease (NAFLD) is a growing public health concern with incompletely understood pathological mechanisms.
  • Long noncoding RNAs (lncRNAs) and messenger RNAs are implicated in NAFLD development, but their specific roles require further elucidation.

Purpose of the Study:

  • To identify abnormally expressed lncRNAs and mRNAs involved in NAFLD pathogenesis.
  • To investigate the functional role of CCAT1 in lipid droplet accumulation and its regulatory mechanism in NAFLD.

Main Methods:

  • Oleic acid (OA)-treated L02 cells were used to assess lncRNA expression and CCAT1 function in vitro.
  • Microarray analysis identified differentially expressed genes (DEGs), with CCAT1-related DEGs verified by weighted correlation network analysis.
  • Interactions between CCAT1, miR-613, and LXRα were examined, including binding verification and expression analysis in NAFLD tissue samples.

Main Results:

  • CCAT1 expression was induced by OA and upregulated in NAFLD clinical samples.
  • Silencing CCAT1 significantly reduced lipid droplet accumulation in vitro, indicating its pro-lipogenic role.
  • CCAT1 was found to increase LXRα transcription by acting as a competing endogenous RNA for miR-613, thereby promoting LXRα expression and lipid droplet formation.

Conclusions:

  • CCAT1 promotes lipid droplet formation and NAFLD progression by upregulating LXRα transcription via the miR-613/CCAT1/LXRα axis.
  • CCAT1 and LXRα represent potential therapeutic targets for managing nonalcoholic fatty liver disease.
Keywords:
LXRαlipid droplet formationlncRNA CCAT1miR-613nonalcoholic fatty liver disease (NAFLD)

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