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.
Highlights
Inhibitors of DNA-binding (ID) proteins are important regulators of cell proliferation and differentiation
We found that ID2 was lowly expressed in Bladder cancer (BCa) tumor tissues, ID2 expression correlated with TNM stage, grade and pathological stage, and that high ID2 expression was positively correlated with overall survival (OS), disease specific survival (DSS), and progress free interval (PFI)
We demonstrated that ID2 can be involved in BCa progression and metastasis through the PI3K/AKT signaling pathway
Summary
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. Bladder cancer (BCa) is one of the tumors with high morbidity and mortality in the urinary system. NMIBC accounts for approximately more than 75% of BCa and the preferred treatment is transurethral resection of bladder tumour (TURBt) (Dy et al, 2017). NMIBC generally has a good prognosis, it has a high recurrence rate and about 10–15% of patients will progress to MIBC in the course of treatment (Ranzi et al, 2017). After the progression of NMIBC to MIBC, radical cystectomy is generally chosen as the treatment modality (Witjes et al, 2021). It is important to explore the mechanisms of BCa progression, discover new biomarkers and identify effective therapeutic targets for BCa
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