Circ_0008305-mediated miR-660/BAG5 axis contributes to hepatocellular carcinoma tumorigenesis

Cancer Med. 2021 Feb;10(3):833-842. doi: 10.1002/cam4.3657. Epub 2021 Jan 22.

Abstract

Increasing circRNAs have attracted a lot of attention because of their significant biological effects in many diseases. It has been reported that circ_0008305 can modulate lung cancer progression. However, the association between circ_0008305 and hepatocellular carcinoma (HCC) needs to be well explored. In this current research, we studied the molecular function and potential mechanism of circ_0008305 in HCC progression. First, it was demonstrated that circ_0008305 was greatly increased in HCC tissues and cells. Moreover, we observed silencing circ_0008305 markedly repressed HCC cells in vitro growth and reduced tumor growth in vivo. Additionally, it was identified that circ_0008305 can act as a sponge of miR-660 while miR-660 targeted Bcl-2-associated athanogene 5 (BAG5). BAG5 belongs to a member of BAG family and it is involved in multiple diseases. We reported that circ_0008305 contributed to the inhibition of miR-660, which resulted in an upregulated expression of BAG5 in HCC. Subsequently, rescue assays were conducted and it was indicated that loss of BAG5 reversed the effects of miR-660 inhibitors on HCC partially. To sum up, it was illustrated by our study that circ_0008305-mediated miR-660-5p/BAG5 axis triggered HCC progression, which could provide a novel insight on the underlying mechanism of HCC progression.

Keywords: BAG5; circ_0008305; hepatocellular carcinoma; miR-660.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinogenesis
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • RNA, Circular / genetics*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Adaptor Proteins, Signal Transducing
  • BAG5 protein, human
  • Biomarkers, Tumor
  • MIRN660 microRNA, human
  • MicroRNAs
  • RNA, Circular