miR-183 regulates autophagy and apoptosis in colorectal cancer through targeting of UVRAG
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Longtao Huangfu1,*, Haihai Liang1,*, Guojie Wang1,*, Xiaomin Su1, Linqiang Li2, Zhimin Du3, Meiyu Hu1, Yuechao Dong1, Xue Bai1, Tianyi Liu1, Baofeng Yang1, Hongli Shan1
1Department 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
2Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
3Institute of Clinical Pharmacy, The 2nd Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P. R. China
*These authors contributed equally to this work
Hongli Shan, e-mail: firstname.lastname@example.org
Keywords: autophagy, UVRAG, miR-183, apoptosis, colorectal cancer
Received: July 08, 2015 Accepted: November 25, 2015 Published: December 22, 2015
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.
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