MiR-218 regulates cisplatin chemosensitivity in breast cancer by targeting BRCA1.
Cisplatin resistance presents a major challenge in the successful treatment of breast cancer, and its mechanism has not been documented well. In this study, to determine the relationship between chemotherapy resistance and microRNA (miRNA) expression during the development of cisplatin resistance in breast cancer, we used microRNA microarrays analysis successfully identified 19 miRNAs that were either overexpressed or underexpressed (8 upregulated and 11 downregulated) in the MCF-7 cell line and its cisplatin-resistant variant MCF-7/DDP. Among them, the miR-218 was most downregulated in cisplatin-resistant cell lines and identified that breast cancer 1 (BRCA1) was the cellular targets of miR-218. In vivo assay also demonstrated that restoring miR-218 expression in MCF-7/DDP cell line could sensitize cells against cisplatin, thereby increasing cisplatin-mediated tumor cell apoptosis and reducing DNA repair. Kaplan-Meier survival analysis indicated that patients with breast cancer display high levels of miR-218 and low levels of BRCA1 expression; these patients may gain the greatest benefits in terms of increased survival when treated with cisplatin. All of these results indicated that miR-218 has a significant function in the development of cisplatin resistance in breast cancer. Restoring miR-218 expression may constitute a novel therapeutic approach by which to increase cisplatin sensitivity in breast cancer.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, People's Republic of China.
Xiao
X
He
Xia
X
Xiao
Lin
L
Dong
Nengbin
N
Wan
Zhengyu
Z
Zhou
Hongwu
H
Deng
Xiefu
X
Zhang
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C547471:MIRN218 microRNA, human; D035683:MicroRNAs; D002945:Cisplatin