title: MiR-133a Is Functionally Involved in Doxorubicin-Resistance in Breast Cancer Cells MCF-7 via Its Regulation of the Expression of Uncoupling Protein 2.
abstract: The development of novel targeted therapies holds promise for conquering chemotherapy resistance, which is one of the major hurdles in current breast cancer treatment. Previous studies indicate that mitochondria uncoupling protein 2 (UCP-2) is involved in the development of chemotherapy resistance in colon cancer and lung cancer cells. In the present study we found that lower level of miR133a is accompanied by increased expression of UCP-2 in Doxorubicin-resistant breast cancer cell cline MCF-7/Dox as compared with its parental cell line MCF-7. We postulated that miR133a might play a functional role in the development of Doxorubicin-resistant in breast cancer cells. In this study we showed that: 1) exogenous expression of miR133a in MCF-7/Dox cells can sensitize their reaction to the treatment of Doxorubicin, which is coincided with reduced expression of UCP-2; 2) knockdown of UCP-2 in MCF-7/Dox cells can also sensitize their reaction to the treatment of Doxorubicin; 3) intratumoral delivering of miR133a can restore Doxorubicin treatment response in Doxorubicin-resistant xenografts in vivo, which is concomitant with the decreased expression of UCP-2. These findings provided direct evidences that the miR133a/UCP-2 axis might play an essential role in the development of Doxorubicin-resistance in breast cancer cells, suggesting that the miR133a/UCP-2 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in breast cancer.
authors.affiliation: Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Surgery, Jiangsu Cancer Hospital and Research Institute, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yu Feng
authors.initials: YF
authors.lastname: Yao
authors.affiliation: Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Sai Nan
authors.initials: SN
authors.lastname: Hu
authors.affiliation: Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D002470:Cell Survival; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics; D000071246:Uncoupling Protein 2
chemical_list: D000903:Antibiotics, Antineoplastic; D007473:Ion Channels; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D024101:Mitochondrial Proteins; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D004317:Doxorubicin