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Method for Measuring the Activity of Deubiquitinating Enzymes in Cell Lines and Tissue Samples
Published on: May 10, 2015
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.
Abstract:
Although a variety of molecular targets have been identified, hepatocellular carcinoma (HCC) remains among the leading causes of death. As functions of they deubiquitinating enzyme Josephin domain containing 2 (JOSD2) in cancers are still poorly understood, we investigated its function and molecular mechanism in the regulation of HCC progression. Here, we indicated that JOSD2 expression is elevated in patient samples with HCC and positively associated with poor prognosis. Moreover, the promoting roles of JOSD2 in HCC cell survival, migration, and invasion were determined using in vitro models. Importantly, a mechanistic study revealed that JOSD2 binds to and decreases the ubiquitination level of catenin beta 1 (CTNNB1), a key component of Wnt signaling, thereby augmenting Wnt pathway transduction. Furthermore, a series of rescue experiments confirmed the significance of CTNNB1 in the modulation of HCC progression by JOSD2. Our study uncovered JOSD2 as a novel prognostic marker for patients with HCC and identified CTNNB1 as a pivotal partner and downstream target protein of JOSD2, which may aid in the development of JOSD2 as a promising molecular target for HCC treatment.
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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