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ID2 Inhibits Bladder Cancer Progression and Metastasis via PI3K/AKT Signaling Pathway
Weipu Mao1,2,3, Keyi Wang4, Si Sun2
1Department of Urology, Shidong Hospital of Yangpu District, Shanghai, China.
Abstract:
Background: Inhibitors of DNA-binding (ID) proteins are important regulators of cell proliferation and differentiation. The aim of this study was to evaluated the role of ID proteins in bladder cancer (BCa) and related molecular mechanisms. Methods: The TCGA database was analyzed for the expression and clinical significance of ID proteins. The expression of ID2 was determined by qRT-PCR, immunohistochemical staining and western blot. The role of ID2 was determined by CCK-8, colony formation, wound healing, transwell and xenograft tumor assays, and the potential mechanism of ID2 in BCa was investigated by RNA sequencing. Results: ID2 expression was significantly downregulated in TCGA database and clinical samples, and high ID2 expression was associated with low-grade tumor staging and correlated with better overall survival, disease specific survival (DSS) and progress free interval (PFI). In vivo and in vitro experiments showed that knockdown of ID2 promoted proliferation, migration, invasion and metastasis of BCa cells, while overexpression of ID2 significantly inhibited cell proliferation, migration, invasion and metastasis. Mechanistically, ID2 acts as a tumor suppressor through PI3K/AKT signaling pathway to inhibit the progression and metastasis of BCa. Conclusion: Our results suggest that ID2 exerts tumor suppressive effects in BCa through PI3K/AKT signaling pathway, and altered ID2 expression can be used as a biomarker of BCa progression and metastasis.
Insights
Inhibitor of DNA-binding 2 (ID2) acts as a tumor suppressor in bladder cancer (BCa). Lower ID2 expression correlates with advanced BCa, while its restoration inhibits cancer progression and metastasis via the PI3K/AKT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Inhibitors of DNA-binding (ID) proteins regulate cell proliferation and differentiation.
- Dysregulation of ID proteins is implicated in various cancers.
Purpose of the Study:
- To investigate the role of ID proteins, specifically ID2, in bladder cancer (BCa).
- To elucidate the molecular mechanisms underlying ID2's function in BCa progression and metastasis.
Main Methods:
- Analysis of TCGA database for ID protein expression and clinical significance.
- Experimental validation of ID2 expression using qRT-PCR, immunohistochemistry, and western blot.
- Functional assays (CCK-8, colony formation, migration, invasion, xenograft) to assess ID2's role in BCa cell behavior.
- RNA sequencing to explore ID2's mechanism of action.
Main Results:
- ID2 expression was significantly downregulated in BCa tissues.
- High ID2 expression correlated with lower tumor grade and improved patient survival outcomes (OS, DSS, PFI).
- ID2 knockdown promoted BCa cell proliferation, migration, invasion, and metastasis, whereas ID2 overexpression inhibited these processes.
Conclusions:
- ID2 functions as a tumor suppressor in bladder cancer.
- ID2 inhibits BCa progression and metastasis by modulating the PI3K/AKT signaling pathway.
- Altered ID2 expression serves as a potential biomarker for BCa progression and metastasis.
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