title: miR-183 regulates autophagy and apoptosis in colorectal cancer through targeting of UVRAG.
abstract: Ultraviolet radiation resistance-associated gene (UVRAG) is a well-known regulator of autophagy by promoting autophagosome formation and maturation. Multiple studies have implicated UVRAG in the pathogenesis of colorectal cancer. However, the mechanisms underlying the regulation of UVRAG are unclear. Here, we describe miR-183 as a new autophagy-inhibiting miRNA. Our results showed that induction of autophagy lead to down-regulation of miR-183 in colorectal cancer cells. And, over-expression of miR-183 resulted in the attenuation of rapamycin- or starvation-induced autophagy in cancer cells, whereas inhibition of endogenous miR-183 stimulated autophagy and apoptosis. Additionally, either autophagy inhibitor 3-MA or pan-caspase inhibitor Z-VAD-FMK respectively or both treatments reversed AMO-183-induced cell death. Further studies showed that UVRAG is a target of miR-183 and as a key regulator promotes autophagy and apoptosis. More importantly, over-expression of UVRAG rescued autophagic activity and induced apoptosis in presence of miR-183. Therefore, the present study investigated the promoting effect of miR-183 on colorectal cancer progression, which was considered to be mediated by autophagy and apoptosis through targeting of UVRAG.
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Longtao
authors.initials: L
authors.lastname: Huangfu
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Haihai
authors.initials: H
authors.lastname: Liang
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Guojie
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Linqiang
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacy, The 2nd Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Du
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Yuechao
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Bai
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C533449:MIRN183 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C408122:UVRAG protein, human
keywords: UVRAG; apoptosis; autophagy; colorectal cancer; miR-183