CircBACH1 (hsa_circ_0061395) promotes hepatocellular carcinoma growth by regulating p27 repression via HuR

J Cell Physiol. 2020 Oct;235(10):6929-6941. doi: 10.1002/jcp.29589. Epub 2020 Jan 31.

Abstract

In recent years, an increasing number of circular RNAs (circRNAs) have been discovered in hepatocellular carcinoma (HCC). However, the functions of most circRNAs require further investigation. Here, we found that circBACH1 was significantly upregulated in HCC tissues and that high circBACH1 levels were closely associated with poor prognosis. In addition, circBACH1 could promote HCC growth by accelerating cell cycle progression in vitro and in vivo. We next investigated the cellular and molecular mechanisms and discovered that circBACH1 inhibited p27 translation, which influenced cell cycle progression. Moreover, we revealed that circBACH1 could combine directly with HuR using RNA immunoprecipitation assays, pull-down assays, and electrophoretic mobility shift assays. The combination of these molecules facilitated HuR translocation from the nucleus to the cytoplasm according to the fluorescence in situ hybridization and immunofluorescence results. Finally, silencing HuR abrogated circBACH1's inhibition of p27 translation and abolished the circBACH1-induced effect on HCC proliferation. In sum, circBACH1 plays a significant role as an oncogene through the circBACH1/HuR/p27 axis in HCC development.

Keywords: HuR; cell cycle; circRNAs; hepatocellular carcinoma; p27.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle / genetics
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics*
  • Cytoplasm / genetics
  • ELAV-Like Protein 1 / genetics*
  • Hep G2 Cells
  • Humans
  • In Situ Hybridization, Fluorescence / methods
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • RNA, Circular / genetics*
  • Up-Regulation / genetics

Substances

  • BACH1 protein, human
  • Basic-Leucine Zipper Transcription Factors
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • RNA, Circular
  • Cyclin-Dependent Kinase Inhibitor p27