hsa_circ_0004018 suppresses the progression of liver fibrosis through regulating the hsa-miR-660-3p/TEP1 axis

Aging (Albany NY). 2020 Jun 25;12(12):11517-11529. doi: 10.18632/aging.103257. Epub 2020 Jun 25.

Abstract

Efforts have been made in the prevention and treatment of liver fibrosis. The inhibition or depletion of the hepatic stellate cells (HSCs) has been considered as a potential approach. Recently, there are numbers of studies about the role of the circular RNA in the disease progression. However, the role of circular RNA in the regulation of HSCs and the progression of liver fibrosis remained elusive. In this study, we constructed a CCl4-induced liver fibrosis mouse model and overexpressed hsa_circ_0004018 in HSCs. Then, salvianolic acid B was used to treat HSCs in vitro. We found that hsa_circ_0004018 is downregulated in liver fibrogenesis. Luciferase reporter assay was performed to verify the interaction of hsa_circ_0004018, hsa-miR-660-3p and TEP1. It showed that hsa_circ_0004018 may act as a sponge of hsa-miR-660-3p, which can target and downregulate the expression of TEP1. hsa_circ_0004018 expressing lentivirus was used to investigate the in-vivo function of hsa_circ_0004018 in CCl4-induced liver fibrosis mice. We also reveal that the hsa_circ_0004018/hsa-miR-660-3p/TEP1 axis contributes to the proliferation and activation of HSCs. In addition, the overexpression of hsa_circ_0004018 alleviated the progression of liver fibrosis. In conclusion, our study highlights hsa_circ_0004018 as a potential biomarker and therapeutic target for liver fibrosis.

Keywords: circular RNA; hepatic stellate cells; liver fibrosis; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzofurans / pharmacology
  • Benzofurans / therapeutic use
  • Biomarkers / metabolism
  • Carbon Tetrachloride / toxicity
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Cells, Cultured
  • Computational Biology
  • Disease Models, Animal
  • Disease Progression
  • Down-Regulation
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / pathology*
  • Humans
  • Liver / drug effects
  • Liver / pathology
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / genetics*
  • Male
  • Mice
  • Mice, Transgenic
  • MicroRNAs / metabolism*
  • Primary Cell Culture
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • RNA-Binding Proteins / genetics*
  • Transfection

Substances

  • Benzofurans
  • Biomarkers
  • MIRN660 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA-Binding Proteins
  • TEP1 protein, human
  • salvianolic acid B
  • Carbon Tetrachloride