title: microRNA-495 promotes bladder cancer cell growth and invasion by targeting phosphatase and tensin homolog.
abstract: Accumulating evidence has linked deregulation of microRNA-495 (miR-495) to tumorigenesis; however, its function in tumor progression is controversial. This work was undertaken to explore the expression and biological roles of miR-495 in bladder cancer. The expression of miR-495 was examined in 67 pairs of bladder cancer and adjacent normal bladder tissues. The roles of miR-495 in bladder cancer cell proliferation and invasion in vitro and tumorigenesis in vivo were determined. Direct target gene(s) mediating the activity of miR-495 in bladder cancer cells was identified. It was found that miR-495 was expressed at greater levels in bladder tissues and cell lines. High expression of miR-495 was significantly associated with larger tumor size, advanced TNM stage, and lymph node metastasis. Overexpression of miR-495 significantly promoted bladder cancer cell proliferation and invasion, whereas inhibition of miR-495 suppressed cell proliferation and invasion. PTEN, a well-defined tumor suppressor was identified to be a target gene of miR-495. A significant inverse correlation between miR-495 and PTEN expression was noted in bladder cancer tissues (r = -0.3094, P = 0.0125). Overexpression of miR-495 led to reduction of PTEN expression in bladder cancer cells. Rescue experiments showed that enforced expression of PTEN impaired miR-495-mediated bladder cancer proliferation and invasion. In vivo mouse studies demonstrated that overexpression of miR-495 accelerated the growth of subcutaneous bladder cancer xenografts, which was associated with downregulation of PTEN. Overall, these findings indicate that miR-495 upregulation contributes to bladder cancer cell growth, invasion, and tumorigenesis by targeting PTEN and offer a potential therapeutic target for bladder cancer.
authors.affiliation: Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Mu
authors.affiliation: Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China. Electronic address: drzhihongliu@163.com.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China.
authors.forename: Le
authors.initials: L
authors.lastname: Tao
authors.affiliation: Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China.
authors.forename: Jifu
authors.initials: J
authors.lastname: Ge
authors.affiliation: Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China. Electronic address: jasonqiu@hotmail.com.
authors.forename: Jianxin
authors.initials: J
authors.lastname: Qiu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000235:genetics*; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology
chemical_list: C577768:MIRN495 microRNA, human; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: Bladder cancer; Growth; Invasion; PTEN; miR-495