MiR-103/107 induces tumorigenicity in bladder cancer cell by suppressing PTEN

Q.-F. Yu, P. Liu, Z.-Y. Li, C.-F. Zhang, S.-Q. Chen, Z.-H. Li, G.-Y. Zhang, J.-C. Li

Department of Urinary Surgery, Ward 2, The First Affiliated Hospital of Xinxiang Medical University, Wei Hui, Xinxiang, Henan Province, China. lijianchang2005@163.com

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• Oncology

OBJECTIVE: MiR-103/107 has been shown to be implicated in the pathogenesis of various malignant diseases. The present study was designed to analyze the expression, function and mechanism of miR-103/107 in the bladder cancer tumorigenesis.

PATIENTS AND METHODS: Bladder cancer tissues and the paired normal tissues were collected during the surgical treatment of radical cystectomy, and the expression of miR-103/107 was measured by quantitative Reverse Transcriptional Polymerase Chain Reaction (RT-PCR). After modulation of miR-103/107 level in bladder cancer cells using antagomiR or mimics, several experimental approaches such as MTT assay, flow cytometry analysis and Western blot have been applied to determine cell viability, cell cycle and protein expression, respectively. Luciferase reporter assay was performed to determine the target of miR-103/107.

RESULTS: miR-103/107 expression is upregulated in the tumor site of bladder cancer specimens, and it is positively associated with tumor stages. Inhibition of miR-103/107 by its antagomiR decreased the cell growth potential and induced cell cycle arrest. Moreover, inhibition of miR-103/107 also suppressed the PI3K/AKT signaling. Further analysis revealed that miR-103/107 directly targets the 3’ untranslated region (UTR) of PTEN mRNA to promote PI3K/AKT signaling, which was corroborated by the negative correlation between miR-103/107 and PTEN in tumor specimens.

CONCLUSIONS: The oncogenic role of miR-103/107 in bladder cancer is revealed for the first time. MiR-103/107 regulates cell proliferation and PI3K/AKT signaling partially through PTEN dependent mechanism. Thus, inhibiting miR-103/107 may be a therapeutic approach for bladder cancer treatment.

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