title: microRNA-21 modulates cell proliferation and sensitivity to doxorubicin in bladder cancer cells.
abstract: 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 determined 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.
authors.affiliation: Department of Urology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tao
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lu
authors.forename: Deyao
authors.initials: D
authors.lastname: Wu
authors.forename: Pengchao
authors.initials: P
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Weijie
authors.initials: W
authors.lastname: Qing
authors.forename: Meilin
authors.initials: M
authors.lastname: Wang
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin