title: miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1.
abstract: MicroRNAs (miRNAs) family, which is involved in cancer development, proliferation, apoptosis, and drug resistance, is a group of noncoding RNAs that modulate the expression of oncogenes and antioncogenes. Doxorubicin is an active cytotoxic agent for breast cancer treatment, but the acquisition of doxorubicin resistance is a common and critical limitation to cancer therapy. The aim of this study was to investigate whether miR-193b mediated the resistance of breast cancer cells to doxorubicin by targeting myeloid cell leukemia-1 (MCL-1). In this study, we found that miR-193b levels were significantly lower in doxorubicin-resistant MCF-7 (MCF-7/DOXR) cells than in the parental MCF-7 cells. We observed that exogenous miR-193b significantly suppressed the ability of MCF-7/DOXR cells to resist doxorubicin. It demonstrated that miR-193b directly targeted MCL-1 3'-UTR (3'-Untranslated Regions). Further studies indicated that miR-193b sensitized MCF-7/DOXR cells to doxorubicin through a mechanism involving the downregulation of MCL-1. Together, our findings provide evidence that the modulation of miR-193b may represent a novel therapeutic target for the treatment of breast cancer.
authors.affiliation: Department of Surgery, The Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China.
authors.forename: Jingpei
authors.initials: J
authors.lastname: Long
authors.affiliation: School of Electronics and Information Engineering, Tongji University, Shanghai 201804, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou 310012, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Xinhua Hospital, School of Medicine, Jiaotong University, Shanghai 200092, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou 310012, China.
authors.forename: Guanmin
authors.initials: G
authors.lastname: Meng
mesh_terms: D020413:3' Untranslated Regions; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000378:metabolism*; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000903:Antibiotics, Antineoplastic; C579095:MCL1 protein, human; C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D011994:Recombinant Proteins; D004317:Doxorubicin