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The Role of OTUD3 as a Novel Oncogenic Driver and Therapeutic Target in Hepatocellular Carcinoma
Lu Lu1, Qifeng Lu1, Jialin Zhang2
1Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong Province, China.
Introduction:
Hepatocellular Carcinoma (HCC) represents a significant health challenge globally, characterized by its high incidence and mortality rates. The exact relationship between ovarian-tumor-domain-containing deubiquitinase 3 (OTUD3) expression and HCC remains inadequately explored, presenting a significant gap in our understanding.
Methods:
This study employed a comprehensive multi-omics approach, integrating expression analysis and functional validation to elucidate the biological roles of OTUD3 in HCC.
Results:
OTUD3 exerted tumor-promoting effects in HCC. Analysis of TCGA data revealed significant OTUD3 overexpression in HCC. OTUD3 drove HCC cell cycle progression by promoting the G1/S transition through interaction with and deubiquitination of minichromosome maintenance complex component 7 (MCM7). In vitro, OTUD3 knockdown suppressed HCC proliferation and migration. In vivo, OTUD3 promoted HCC progression in a Diethylnitrosamine (DEN)-induced mouse model.
Discussion:
These findings establish OTUD3 as a multifunctional oncoprotein driving HCC progression primarily through tumor-intrinsic mechanisms. Its expression in tumor-infiltrating immune cells also suggests a potential role in the immune microenvironment.
Conclusion:
These findings establish the OTUD3-MCM7 axis as a mechanistic link in HCC cell cycle dysregulation and suggest that targeting this interaction may offer a therapeutic strategy.
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