4.5 Article

microRNA-21 modulates cell proliferation and sensitivity to doxorubicin in bladder cancer cells

Journal

ONCOLOGY REPORTS
Volume 25, Issue 6, Pages 1721-1729

Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/or.2011.1245

Keywords

microRNA-21; bladder cancer; doxorubicin; chemosensitivity; PTEN

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Transitional cell carcinomas (TCCs) of the urinary bladder are common malignancies with a high recurrence rate. Since microRNA-21 (miR-21) may contribute to tumorigenesis and chemoresistance in many cancer types, we aimed to investigate its efficacy in TCCs. The expression of miR-21 and its target PTEN was dei:ermined by real-time qRT-PCR and Western blotting, respectively in tumor tissues as well as adjacent non-tumor mucosa. The effect of miR-21 on cell proliferation and chemosensitivity to doxorubicin were measured using the MTT method. Cell apoptosis induced by doxorubicin was investigated using flow cytometry in the T24 cell line. BCL-2, AKT and pAKT were detected by Western blotting for analysis of potential mechanisms. miR-21 was significantly up-regulated in tumor tissues while PTEN was expressed in lower levels compared to non-tumor tissues. A negative correlation between expression of miR-21 and PTEN was established in vivo. Cell proliferation and chemoresistance to doxorubicin were promoted by overexpression of miR-21 in T24 cells. BCL-2 up-regulation could be achieved by miR-21 overexpression, which prevented T24 cells from apoptosis induced by doxorubicin. Furthermore, the miR-21 induced BCL-2 up-regulation could be cancelled by the PI3K inhibitor LY294002. These data verified the oncogenic role of miR-21 in TCCs and may usher in new therapeutic strategies in treating this disease.

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