Circ_0007429/miR-637/TRIM71/Ago2 axis participates in the regulation of proliferation, migration, invasion, apoptosis, and aerobic glycolysis of HCC

Mol Carcinog. 2023 Jun;62(6):820-832. doi: 10.1002/mc.23526. Epub 2023 Mar 15.

Abstract

CircRNAs play an important role in the progression of hepatocellular carcinoma (HCC), however, the role of circ_0007429 in HCC remains unknown. Using bioinformatics tools, we selected circ_0007429 that was most highly expressed in HCC tissues and investigated its role in HCC progression. Immunohistochemistry, plasmid transfection, real-time quantitative PCR, and western blot analysis were used to identify the relationship between circ_0007429 and its potential target, miR-637, and TRIM71. The regulatory effect of circ_0007429 on miR-637/TRIM71/Ago2 signaling and its key role in HCC progression were studied in vitro. A nude mouse xenograft model was used to examine tumor growth in vivo. Circ_0007429 and TRIM71 expression were upregulated, while miR-637 expression was downregulated in HCC tissues and cells compared with their expression in control groups. Knockdown of circ_0007429 enhanced apoptosis in HCC cells, while impeded proliferation, migration, invasion, and aerobic glycolysis, which were reversed by miR-637 inhibitor. High levels of circ_0007429 correlated with a poor survival rate of HCC patients. Additionally, circ_0007429 interfering inhibited tumor growth in vivo. TRIM71 directly bound to miR-637 and inhibited Ago2 expression. Moreover, circ_0007429 promotes aerobic glycolysis in HCC cells through the miR/TRIM71/Ago2 axis. Circ_0007429 promotes HCC progression by promoting cell proliferation, migration, invasion, and aerobic glycolysis and by inhibiting cell apoptosis through the miR/TRIM71/Ago2 axis. These results provide molecular insights into the mechanism of HCC and suggest that circ_0007429 could be a therapeutic target for HCC.

Keywords: Ago2; TRIM71; circ_0007429; hepatocellular carcinoma; miR-637.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Hepatocellular* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Glycolysis / genetics
  • Humans
  • Liver Neoplasms* / genetics
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • Tripartite Motif Proteins / genetics
  • Ubiquitin-Protein Ligases / genetics

Substances

  • MicroRNAs
  • TRIM71 protein, human
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • MIRN637 microRNA, human