Deubiquitinating enzyme JOSD2 promotes hepatocellular carcinoma progression through interacting with and inhibiting

Yao Huang1,2, Jianxing Zeng1, Teng Liu1

  • 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Insights

Elevated Josephin domain containing 2 (JOSD2) promotes hepatocellular carcinoma (HCC) progression by stabilizing catenin beta 1 (CTNNB1). JOSD2 is a potential prognostic marker and therapeutic target for HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) remains a significant cause of cancer mortality despite advances in molecularly targeted therapies.
  • The specific roles of the deubiquitinating enzyme Josephin domain containing 2 (JOSD2) in cancer progression are not well-defined.

Purpose of the Study:

  • To investigate the function and molecular mechanism of JOSD2 in regulating hepatocellular carcinoma (HCC) progression.
  • To evaluate JOSD2 as a potential prognostic marker and therapeutic target for HCC.

Main Methods:

  • Analysis of JOSD2 expression in HCC patient samples.
  • In vitro studies to assess the effects of JOSD2 on HCC cell survival, migration, and invasion.
  • Mechanistic studies involving JOSD2 binding to and deubiquitination of catenin beta 1 (CTNNB1).
  • Rescue experiments to confirm the role of CTNNB1.

Main Results:

  • JOSD2 expression is significantly upregulated in HCC tissues and correlates with poor patient prognosis.
  • JOSD2 enhances HCC cell survival, migration, and invasion in vitro.
  • JOSD2 directly binds to CTNNB1, reduces its ubiquitination, and enhances Wnt pathway signaling.
  • CTNNB1 is essential for JOSD2-mediated HCC progression.

Conclusions:

  • JOSD2 is a novel prognostic biomarker for HCC.
  • JOSD2 promotes HCC progression by targeting CTNNB1 and activating Wnt signaling.
  • JOSD2 represents a promising molecular target for future HCC therapeutic strategies.

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