title: MiR-363 sensitizes cisplatin-induced apoptosis targeting in Mcl-1 in breast cancer.
abstract: Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic Bcl-2 family member that is often overexpressed in breast tumors, and has been reported to have an important role in regulating drug resistance in various types of cancer including breast cancer. However, the mechanisms underlying the aberrant expression of Mcl-1 are still unclear. In this study, we used bioinformatics, cellular, and molecular methods to predict and prove that miR-363 directly targeted Mcl-1 3'-UTR (3'-untranslated regions) and caused downregulation of Mcl-1 in breast cancer. Resistance to chemotherapy is a major barrier for the effective treatment for advanced breast cancer, but our study indicated that miR-363 reversed the resistance of the breast cancer cell line MDA-MB-231 to the chemotherapeutic agent cisplatin (CDDP). In addition, transfection of breast cancer cells with Mcl-1 expression plasmid abolished the sensitization effect of miR-363 to cisplatin-inducing cytotoxicity. In summary, our study showed that miR-363 was a negative regulator of Mcl-1 expression, and the combination of miR-363 and cisplatin may be a novel approach in the treatment for breast cancer.
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.
authors.forename: Ruiguang
authors.initials: R
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Dong
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.forename: Xiu
authors.initials: X
authors.lastname: Nie
mesh_terms: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001943:Breast Neoplasms; D045744:Cell Line, Tumor / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics*; D058990:Molecular Targeted Therapy; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C579095:MCL1 protein, human; C574861:MIRN363 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D002945:Cisplatin