MicroRNA-200a induces apoptosis by targeting ZEB2 in alcoholic liver disease

Cell Cycle. 2018;17(2):250-262. doi: 10.1080/15384101.2017.1417708. Epub 2018 Jan 15.

Abstract

ABSTRAT Alcoholic liver disease (ALD) and its complication continued to be a major health problem throughout the world. Increasing evidence suggests that microRNA (miRNA) that regulate apoptosis, inflammation and lipid metabolism are affected by alcohol in ALD. MiR-200a has emerged as a major regulator in several liver diseases, but its role in ALD has not been elucidated. The aim of this study is to figure out the biological function of miR-200a in ALD and to explore its underlying mechanism. The expression pattern of miR-200a were analyzed in vitro and in vivo, we showed that miR-200a was up-regulated in ALD in AML-12 and primary hepatocyte. We then examined it's effect on cell apoptosis and identified zinc finger E-box binding homeobox 2 (ZEB2; also known as SIP1) as a direct target gene of miR-200a. Furthermore, reintroduction of ZEB2 could reverse the pro-apoptosis of miR-200a on AML-12. Taken together, our study demonstrated that miR-200a regulates the apoptosis of hepatocyte in ALD by directly target ZEB2, both of which could serve as new therapeutic targets for ALD.

Keywords: ALD; Alcoholic liver disease; Apoptosis; ZEB2; miR-200a; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Line
  • Ethanol / toxicity
  • Hepatocytes / cytology
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Liver Diseases, Alcoholic / genetics*
  • Liver Diseases, Alcoholic / metabolism
  • Liver Diseases, Alcoholic / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / metabolism*
  • Zinc Finger E-box Binding Homeobox 2 / genetics*
  • Zinc Finger E-box Binding Homeobox 2 / metabolism

Substances

  • MicroRNAs
  • Mirn200 microRNA, mouse
  • ZEB2 protein, mouse
  • Zinc Finger E-box Binding Homeobox 2
  • Ethanol

Grants and funding

National Natural Science Foundation of China [grant number 81473268]; Anhui University of Science and Technology [grant number 1704a0802161].