The interplay of microRNAs and transcription factors in autophagy regulation in nonalcoholic fatty liver disease

Exp Mol Med. 2021 Apr;53(4):548-559. doi: 10.1038/s12276-021-00611-0. Epub 2021 Apr 20.

Abstract

The autophagy-lysosomal degradation system has an important role in maintaining liver homeostasis by removing unnecessary intracellular components. Impaired autophagy has been linked to nonalcoholic fatty liver disease (NAFLD), which includes hepatitis, steatosis, fibrosis, and cirrhosis. Thus, gaining an understanding of the mechanisms that regulate autophagy and how autophagy contributes to the development and progression of NAFLD has become the focus of recent studies. Autophagy regulation has been thought to be primarily regulated by cytoplasmic processes; however, recent studies have shown that microRNAs (miRNAs) and transcription factors (TFs) also act as key regulators of autophagy by targeting autophagy-related genes. In this review, we summarize the miRNAs and TFs that regulate the autophagy pathway in NAFLD. We further focus on the transcriptional and posttranscriptional regulation of autophagy and discuss the complex regulatory networks involving these regulators in autophagy. Finally, we highlight the potential of targeting miRNAs and TFs involved in the regulation of autophagy for the treatment of NAFLD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Biomarkers
  • Disease Susceptibility
  • Gene Expression Regulation*
  • Humans
  • MicroRNAs / genetics*
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Non-alcoholic Fatty Liver Disease / metabolism*
  • Non-alcoholic Fatty Liver Disease / pathology
  • RNA Interference
  • Transcription Factors / metabolism*

Substances

  • Autophagy-Related Proteins
  • Biomarkers
  • MicroRNAs
  • Transcription Factors