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Biochem Biophys Res Commun. 2017 Feb 5;483(2):867-873. doi: 10.1016/j.bbrc.2017.01.019. Epub 2017 Jan 6.

microRNA-495 promotes bladder cancer cell growth and invasion by targeting phosphatase and tensin homolog.

Author information

1
Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China.
2
Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China. Electronic address: drzhihongliu@163.com.
3
Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai, PR China. Electronic address: jasonqiu@hotmail.com.

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.

KEYWORDS:

Bladder cancer; Growth; Invasion; PTEN; miR-495

PMID:
28069380
DOI:
10.1016/j.bbrc.2017.01.019
[Indexed for MEDLINE]

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