title: miR-214 promotes apoptosis and sensitizes breast cancer cells to doxorubicin by targeting the RFWD2-p53 cascade.
abstract: miR-214 is involved in numerous physiological and pathological processes including tumorigenesis. However, the function of miR-214 in the development and treatment of breast cancer remains elusive. In this study, we report that miR-214 is strikingly down-regulated in breast cancer cell lines and clinical samples, particularly, in the doxorubicin resistant tumor tissues. Remarkably, restoration of miR-214 expression induces apoptosis and sensitizes the MCF7 cells sustaining wild-type p53, but not the p53 null MDA-MB-157 cells, to doxorubicin. Furthermore, we reveal that miR-214 directly down-regulates the expression of RFWD2, also known as COP1, an E3 ligase targeting the tumor suppressor p53 for proteasomal degradation. In addition, RFWD2 protein levels are reversely correlated with miR-214 expression levels in breast cancer tissues. Moreover, ectopic expression of RFWD2 markedly abolishes miR-214-triggered apoptosis of MCF7 cells. In conclusion, miR-214 functions as a tumor suppressor by regulating the RFWD2-p53 cascade, thus delivery of miR-214 analogs could be a potential adjunct therapy in breast cancer harboring wild type p53.
authors.affiliation: Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jiaxuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gong
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Qingsongg
authors.initials: Q
authors.lastname: Xi
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: turnface@126.com.
authors.forename: Tengfei
authors.initials: T
authors.lastname: Chao
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D035683:MicroRNAs; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; C547397:MIRN214 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; C471981:COP1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: Apoptosis; Breast cancer; Chemotherapy; RFWD2; miR-214