title: Enforced expression of miR-101 enhances cisplatin sensitivity in human bladder cancer cells by modulating the cyclooxygenase-2 pathway.
abstract: 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.
authors.affiliation: Department of Urology, Danyang People's Hospital, Zhenjiang, Jiangsu, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Bu
authors.affiliation: Department of Central Laboratory, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Central Laboratory, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Central Laboratory, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, P.R. China.
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Oncology, Taixing People's Hospital, Taixing, Jiangsu, P.R. China.
authors.forename: Yangchen
authors.initials: Y
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000633:toxicity*; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000627:therapeutic use; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016415:Sequence Alignment; D014183:Transplantation, Heterologous; D015854:Up-Regulation / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D002945:Cisplatin