title: MiR-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1.
abstract: Radioresistance is a major challenge during the treatment of breast cancer. A further understanding of the mechanisms of radioresistance could provide strategies to address this challenge. In our study, we compared the expression of miR-200c in four distinct breast cancer cell lines: two representative basal cancer cells (MDA-MB-231 and BT549) vs. two representative luminal cancer cells (MCF-7 and BT474). The results revealed practically lower expression of miR-200c in the two basal cancer cell lines and higher expression of miR-200c in luminal cancer cells compared to the normal breast epithelial cell line MCF-10A. Ectopic expression of miR-200c in MDA-MB-231 cells inhibited irradiation-induced autophagy and sensitized the breast cancer cells to irradiation. We also identified UBQLN1 as a direct functional target of miR-200c involved in irradiation-induced autophagy and radioresistance. In 35 human breast cancer tissue samples, we detected an inverse correlation between the expression of miR-200c vs. UBQLN1 and LC3. These results indicate that the identified miR-200c/UBQLN1-mediated autophagy pathway may help to elucidate radioresistance in human breast cancer and might represent a therapeutic strategy.
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China.
authors.forename: Quanquan
authors.initials: Q
authors.lastname: Sun
authors.forename: Tongxin
authors.initials: T
authors.lastname: Liu
authors.forename: Yawei
authors.initials: Y
authors.lastname: Yuan
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Guo
authors.forename: Guozhu
authors.initials: G
authors.lastname: Xie
authors.forename: Shasha
authors.initials: S
authors.lastname: Du
authors.forename: Xiaoshan
authors.initials: X
authors.lastname: Lin
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Xu
authors.forename: Minfeng
authors.initials: M
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.forename: Longhua
authors.initials: L
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000528:radiation effects; D001343:Autophagy / Q000528:radiation effects*; D000071183:Autophagy-Related Proteins; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D002352:Carrier Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C477012:MAP1LC3A protein, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C107792:UBQLN1 protein, human; D008156:Luciferases
keywords: UBQLN1; autophagy; breast cancer; miR-200c; radioresistance