miR-202 Inhibits Cell Proliferation, Migration, and Invasion by Targeting Epidermal Growth Factor Receptor in Human
Liqing Zhang1, Jianjiang Xu2, Gaodi Yang1
1Department of Urology Surgery, General Hospital of Jinan Military Command, Jinan, Shandong, P.R. China.
Abstract:
Recent studies have demonstrated that miR-202 is associated with several types of cancer; however, the expression and function of miR-202 have not been investigated in bladder cancer. We analyzed the expression of miR-202 in bladder cancer tissues and adjacent noncancerous tissues. The effect of miR-202 on the proliferation, migration, and invasion was evaluated by in vitro assays. The target gene of miR-202 was assessed by luciferase reporter assay. In this study, miR-202 was found to be significantly downregulated in bladder cancer cell lines and tissues and was highly correlated with the T classification, N classification, grade, and recurrence. Ectopic expression of miR-202 suppressed cell viability, colony formation, cell migration, and invasion in vitro and inhibited xenograft tumor growth in vivo. Inversely, downregulation of miR-202 had contradictory effects. The 3'-untranslated region (3'-UTR) of epidermal growth factor receptor (EGFR) was identified as a direct target of miR-202 using luciferase reporter assays, and knockdown of EGFR enhanced miR-202-inhibited cell proliferation, migration, and invasion. In conclusion, miR-202 suppresses bladder cancer carcinogenesis and progression by targeting EGFR, thereby representing a potential target for miRNA-based therapy for bladder cancer in the future.
Insights
MicroRNA-202 (miR-202) is downregulated in bladder cancer, suppressing tumor growth and progression. Targeting miR-202 and its downstream effects on epidermal growth factor receptor (EGFR) offers a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-202 (miR-202) has been implicated in various cancers, but its role in bladder cancer remains unexplored.
- Understanding miR-202's expression and function is crucial for developing novel bladder cancer therapies.
Purpose of the Study:
- To investigate the expression profile of miR-202 in bladder cancer.
- To elucidate the functional role of miR-202 in bladder cancer cell proliferation, migration, and invasion.
- To identify the direct molecular targets of miR-202 in bladder cancer.
Main Methods:
- Quantitative real-time PCR to analyze miR-202 expression in bladder cancer tissues and cell lines.
- In vitro assays (proliferation, migration, invasion) to assess miR-202's functional impact.
- Luciferase reporter assays to validate miR-202's direct targeting of the epidermal growth factor receptor (EGFR) 3'-UTR.
- In vivo xenograft models to evaluate miR-202's effect on tumor growth.
Main Results:
- miR-202 was significantly downregulated in bladder cancer tissues and cell lines, correlating with advanced T classification, N classification, grade, and recurrence.
- Overexpression of miR-202 inhibited bladder cancer cell proliferation, colony formation, migration, and invasion in vitro, and suppressed tumor growth in vivo.
- Epidermal growth factor receptor (EGFR) was identified as a direct target of miR-202.
- Knockdown of EGFR reversed the suppressive effects of miR-202 on cancer cell behaviors.
Conclusions:
- miR-202 acts as a tumor suppressor in bladder cancer by targeting EGFR.
- Downregulation of miR-202 promotes bladder cancer initiation and progression.
- miR-202 represents a promising therapeutic target for miRNA-based bladder cancer treatment.
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