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TRIM21 is critical in regulating hepatocellular carcinoma growth and response to therapy by altering the MST1/YAP

Bo Shu1, Yingxia Zhou2, Guoqiong Lei3

  • 1Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Cancer Science
|March 13, 2024
PubMed

Insights

This study reveals that elevated TRIM21 protein promotes liver cancer (hepatocellular carcinoma) growth and chemoresistance by activating the YAP pathway. Reducing TRIM21 hinders cancer progression and increases sensitivity to treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Liver cancer, particularly hepatocellular carcinoma (HCC), has a poor prognosis globally.
  • The protein TRIM21 is implicated in various cancer hallmarks but its role in HCC tumorigenesis is unclear.
  • TRIM21 is a potential prognostic marker for HCC, necessitating mechanistic investigation.

Purpose of the Study:

  • To elucidate the mechanism by which TRIM21 influences hepatocellular carcinoma (HCC) progression and chemoresistance.
  • To investigate the role of TRIM21 in regulating the Hippo signaling pathway in HCC.
  • To identify TRIM21 as a potential therapeutic target for liver cancer.

Main Methods:

  • Quantification of TRIM21 protein levels in human HCC tissues.
  • TRIM21 knockdown experiments in HCC cell lines.
  • Analysis of YAP translocation and MST1 ubiquitination and degradation.
  • Investigating the effects of MST1 knockdown and YAP overexpression on HCC growth and chemosensitivity.

Main Results:

  • TRIM21 protein levels are elevated in HCC and correlate with disease progression and poor survival.
  • TRIM21 knockdown inhibits HCC cell growth, metastasis, and enhances sorafenib toxicity.
  • TRIM21 promotes HCC by inducing MST1 degradation, leading to YAP activation.
  • MST1 knockdown or YAP overexpression rescues the effects of TRIM21 knockdown.

Conclusions:

  • TRIM21 promotes HCC growth and chemoresistance through MST1-mediated YAP activation, a novel mechanism involving the Hippo pathway.
  • TRIM21 is a critical factor in HCC progression and represents a potential therapeutic target.
Keywords:
E3 ubiquitin ligasechemosensitivitysorafenibtherapeutic target

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