Hsa_circ_0026134 expression promoted TRIM25- and IGF2BP3-mediated hepatocellular carcinoma cell proliferation and invasion via sponging miR-127-5p

Biosci Rep. 2020 Jul 31;40(7):BSR20191418. doi: 10.1042/BSR20191418.

Abstract

Increasing evidence shows that circular RNAs (circRNAs) play a regulatory role in cancer. In the present study, we aimed to investigate the characteristics and effects of hsa_circ_0026134 in hepatocellular carcinoma (HCC). We investigated hsa_circ_0026134 expression in 20 pairs of clinical tissues from HCC patients; expression of hsa_circ_0026134 in different cell lines; effect of hsa_circ_0026134 on proliferation and invasion of HCC cell lines; and the regulatory mechanisms and interactions among hsa_circ_0026134, miR-127-5p, tripartite motif-containing protein 25 (TRIM25) and insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3). hsa_circ_0026134 expression was increased in HCC samples and cell lines. Down-regulation of hsa_circ_0026134 attenuated HCC cell proliferation and metastatic properties. Micro (mi)RNA (miR)-127-5p was sponged by hsa_circ_0026134. Rescue experiments indicated that inhibition of miR-127-5p expression promoted cell proliferation and invasion even after hsa_circ_0026134 silencing. TRIM25 and IGF2BP3 were targets of miR-127-5p. Overexpression of TRIM25 or IGF2BP3 promoted cell proliferation and invasion in cells overexpressing miR-127-5p. Down-regulation of hsa_circ_0026134 suppressed TRIM25- and IGF2BP3-mediated HCC cell proliferation and invasion via promotion of miR-127-5p expression, which have been confirmed by luciferase reporter assay. The present study provides a new treatment target for HCC.

Keywords: IGF2BP3; TRIM25; hepatocellular carcinoma; hsa_circ_0026134; miR-127-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • RNA, Circular / antagonists & inhibitors
  • RNA, Circular / metabolism*
  • RNA-Binding Proteins / genetics
  • Transcription Factors / genetics
  • Tripartite Motif Proteins / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Xenograft Model Antitumor Assays

Substances

  • IGF2BP3 protein, human
  • MIRN127 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA-Binding Proteins
  • Transcription Factors
  • Tripartite Motif Proteins
  • TRIM25 protein, human
  • Ubiquitin-Protein Ligases