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OTUD4: A Potential Prognosis Biomarker for Multiple Human Cancers
Xiaohui Zhao1, Xiaobo Su1, Lu Cao2
1GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou 511436, People's Republic of China.
Deubiquitinase OTU domain containing 4 (OTUD4) is downregulated in many cancers, predicting poor prognosis. Overexpression of OTUD4 inhibits cancer cell growth and invasion by impacting the AKT signaling pathway, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Deubiquitinase OTU domain containing 4 (OTUD4) is a K48-specific deubiquitinase involved in DNA damage repair.
- The role of OTUD4 in human cancers, including its expression, prognostic significance, and biological functions, remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression level, prognostic value, and biological function of OTUD4 in various human cancers.
- To elucidate the underlying molecular mechanisms of OTUD4 in cancer, particularly its association with the AKT signaling pathway.
Main Methods:
- Analysis of OTUD4 mRNA expression and prognostic value using the GEPIA and TCGA databases.
- Functional assays (MTT, Transwell, 3D culture) to assess OTUD4's role in breast, liver, and lung cancer cells.
- Gene Set Enrichment Analysis (GSEA) to explore the correlation between OTUD4 and apoptosis and AKT signaling pathways.
Main Results:
- OTUD4 mRNA expression was significantly downregulated across multiple human cancer types.
- Lower OTUD4 expression correlated with poor prognosis in breast, esophageal, liver, lung, and ovarian cancers.
- OTUD4 overexpression suppressed proliferation, migration, and invasion in breast, liver, and lung cancer cells by inhibiting the AKT signaling pathway.
Conclusions:
- OTUD4 functions as a tumor suppressor in breast, liver, and lung cancers.
- OTUD4 overexpression inhibits cancer progression via promoting apoptosis and suppressing the AKT pathway.
- OTUD4 represents a potential prognostic biomarker and therapeutic target for multiple human cancers.
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