Targeting TRIM54/Axin1/β-Catenin Axis Prohibits Proliferation and Metastasis in Hepatocellular Carcinoma

Jinrong Zhu1, Yongqi Wu1, Shaoxi Lao1

  • 1Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.

Frontiers in Oncology
|December 27, 2021
PubMed

Insights

Overexpression of TRIM54 promotes hepatocellular carcinoma (HCC) progression by degrading Axin1 and activating the wnt/β-catenin pathway. Inhibiting TRIM54 or this pathway suppresses HCC growth, suggesting a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Dysregulation of ubiquitin-mediated degradation is implicated in diseases.
  • The role of ubiquitin ligases in hepatocellular carcinoma (HCC) is not fully understood.

Purpose of the Study:

  • To investigate the function and molecular mechanisms of TRIM54 in HCC progression.
  • To explore TRIM54 as a potential therapeutic target for HCC.

Main Methods:

  • Assessed TRIM54 expression in HCC tissues.
  • Utilized in vitro and in vivo models to study TRIM54's effects on proliferation and metastasis.
  • Investigated the interaction between TRIM54 and Axin1 using biochemical assays.
  • Examined the impact of TRIM54 on wnt/β-catenin signaling.

Main Results:

  • TRIM54 overexpression correlates with HCC progression, enhancing proliferation and lung metastasis.
  • TRIM54 directly interacts with Axin1, promoting its proteasomal degradation.
  • Sustained activation of wnt/β-catenin signaling was observed in HCC cells overexpressing TRIM54.
  • Inhibition of wnt/β-catenin signaling suppressed TRIM54-induced proliferation.

Conclusions:

  • TRIM54 acts as an oncogenic gene in HCC.
  • The TRIM54/Axin1/β-catenin axis is crucial for HCC progression.
  • Targeting this axis offers a potential therapeutic strategy for HCC.

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