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MicroRNA-mRNA functional pairs for cisplatin resistance in ovarian cancer cells
Authors:Mei Liu  Xin Zhang  Chen-Fei Hu  Qing Xu  Hong-Xia Zhu  Ning-Zhi Xu
Institution:Mei Liu(Laboratory of Cel and Molecular Biology & State Key Laboratory of Molecular 0ncology, Cancer Institute&Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical college, Beijing 100021, P. R. China);Xin Zhang(Department of 0bstetrics and Gynecology, China Meitan General Hospital, Beijing 100021, P. R. China);Chen-Fei Hu(Laboratory of Cel and Molecular Biology & State Key Laboratory of Molecular 0ncology, Cancer Institute&Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical college, Beijing 100021, P. R. China);Qing Xu(Laboratory of Cel and Molecular Biology & State Key Laboratory of Molecular 0ncology, Cancer Institute&Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical college, Beijing 100021, P. R. China);Hong-Xia Zhu(Laboratory of Cel and Molecular Biology & State Key Laboratory of Molecular 0ncology, Cancer Institute&Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical college, Beijing 100021, P. R. China);Ning-Zhi Xu(Laboratory of Cel and Molecular Biology & State Key Laboratory of Molecular 0ncology, Cancer Institute&Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical college, Beijing 100021, P. R. China);
Abstract:Ovarian cancer is the leading cause of death in women worldwide. Cisplatin is the core of first-line chemotherapy for patients with advanced ovarian cancer. Many patients eventually become resistant to cisplatin, diminishing its therapeutic effect. MicroRNAs (miRNAs) have critical functions in diverse biological processes. Using miRNA profiling and polymerase chain reaction validation, we identified a panel of differentially expressed miRNAs and their potential targets in cisplatin-resistant SKOV3/DDP ovarian cancer cells relative to cisplatin-sensitive SKOV3 parental cells. More specifically, our results revealed significant changes in the expression of 13 of 663 miRNAs analyzed, including 11 that were up-regulated and 2 that were down-regulated in SKOV3/DDP cells with or without cisplatin treatment compared with SKOV3 cells with or without cisplatin treatment. miRNA array and mRNA array data were further analyzed using Ingenuity Pathway Analysis software. Bioinformatics analysis suggests that the genes ANKRD17, SMC1A, SUMO1, GTF2H1, and TP73, which are involved in DNA damage signaling pathways, are potential targets of miRNAs in promoting cisplatin resistance. This study highlights candidate miRNA-mRNA interactions that may contribute to cisplatin resistance in ovarian cancer.
Keywords:Ovarian cancer  cisplatin resistance  miRNA  TP
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