Targeting MED8 enhances sorafenib sensitivity in hepatocellular carcinoma by disrupting epithelial-mesenchymal

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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis

Published on: September 12, 2019

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Ming Li1,2, Xiaoxiang You1,2, Tinghao Yuan1,2

  • 1Department of Hepatobiliary Tumor Surgery, Department of Interventional Therapy, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, Nanchang, Jiangxi Province, People's Republic of China.

Journal of Enzyme Inhibition and Medicinal Chemistry
|October 21, 2025
PubMed

Insights

Hepatocellular carcinoma (HCC) exhibits sorafenib resistance. This study reveals MED8 enhances this resistance by stabilizing TRIP4, suggesting the MED8-TRIP4 axis as a therapeutic target for HCC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Resistance Research

Background:

  • Hepatocellular carcinoma (HCC) is a lethal cancer with poor outcomes due to sorafenib resistance.
  • The role of MED8 in HCC drug resistance remains largely unexplored.
  • MED8 is implicated in enhancing tumor resistance to various drugs.

Purpose of the Study:

  • To investigate the role of MED8 in sorafenib resistance in HCC.
  • To elucidate the underlying molecular mechanisms involving MED8 in HCC progression and drug resistance.

Main Methods:

  • Comparative analysis of MED8 expression in HCC tissues versus noncancerous tissues.
  • Functional assays including cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) analysis.
  • Investigation of the interaction between MED8 and TRIP4, including protein levels and ubiquitination.

Main Results:

  • Significantly higher MED8 expression in HCC tissues, correlating with poorer overall survival.
  • MED8 knockdown inhibited HCC cell proliferation, EMT, promoted apoptosis, and increased sorafenib sensitivity.
  • MED8 interacts with TRIP4, reducing its ubiquitination and stabilizing its levels, thereby promoting EMT.

Conclusions:

  • The MED8-TRIP4 axis is a key driver of sorafenib resistance in HCC.
  • Targeting the MED8-TRIP4 interaction presents a potential therapeutic strategy for overcoming sorafenib resistance in HCC.
Keywords:
MED8Sorafenib-resistantTRIP4epithelial–mesenchymal transitionubiquitination

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