期刊
MOLECULAR MEDICINE REPORTS
卷 10, 期 4, 页码 2203-2209出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2014.2455
关键词
miR-101; cyclooxygenase-2; bladder cancer
资金
- Science and Technology Support Plan of Zhenjiang City [FZ2012003]
Alterations in microRNA (miRNA) expression have been shown to be involved in the tumor response to chemotherapy. However, the possible role of miR-101 in cisplatin sensitivity in human bladder cancer cells remains unclear. In this study, quantitative polymerase chain reaction and western blotting were utilized to determine the expression profiles of miR-101 and cyclooxygenase-2 (COX-2) in human bladder cancer cells. The effect of miR-101 and small interfering RNA (siRNA) against COX-2 on cell viability was evaluated using MTT assays, and apoptosis levels were determined using fluorescence-activated cell sorting analysis of Annexin V/propidium iodide-stained cells. Luciferase reporter plasmids were constructed to confirm direct targeting. This study found that the expression of miR-101 was downregulated in the cisplatin-resistant cell line T24/CDDP as compared with that in the parental line, T24. Furthermore, overexpression of miR-101 significantly increased the anti-proliferative effects and apoptosis induced by cisplatin, whereas knockdown of miR-101 significantly decreased the anti-proliferative effects and apoptosis induced by cisplatin. In addition, downregulation of miR-101 induced cell survival and cisplatin resistance through the upregulation of COX-2 expression. Luciferase gene reporter assays confirmed that COX-2 was a direct target gene of miR-101. Inhibition of COX-2 using COX-2 siRNA abrogated the cisplatin resistance induced by miR-101 downregulation. These results suggest that miR-101 may provide a novel mechanism for understanding cisplatin resistance in bladder cancer by modulating the COX-2 pathway.
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