Suppressing MTERF3 inhibits proliferation of human hepatocellular carcinoma via ROS-mediated p38 MAPK activation

Commun Biol. 2024 Jan 5;7(1):18. doi: 10.1038/s42003-023-05664-7.

Abstract

Mitochondrial transcription termination factor 3 (MTERF3) negatively regulates mitochondrial DNA transcription. However, its role in hepatocellular carcinoma (HCC) progression remains elusive. Here, we investigate the expression and function of MTERF3 in HCC. MTERF3 is overexpressed in HCC tumor tissues and higher expression of MTERF3 positively correlates with poor overall survival of HCC patients. Knockdown of MTERF3 induces mitochondrial dysfunction, S-G2/M cell cycle arrest and apoptosis, resulting in cell proliferation inhibition. In contrast, overexpression of MTERF3 promotes cell cycle progression and cell proliferation. Mechanistically, mitochondrial dysfunction induced by MTERF3 knockdown promotes ROS accumulation, activating p38 MAPK signaling pathway to suppress HCC cell proliferation. In conclusion, ROS accumulation induced by MTERF3 knockdown inhibits HCC cell proliferation via p38 MAPK signaling pathway suggesting a promising target in HCC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Liver Neoplasms* / pathology
  • Mitochondrial Diseases*
  • Mitochondrial Proteins* / genetics
  • Reactive Oxygen Species / metabolism
  • Transcription Factors* / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • p38 Mitogen-Activated Protein Kinases
  • Reactive Oxygen Species
  • MTERF3 protein, human
  • Transcription Factors
  • Mitochondrial Proteins