role of microrna-182 in posterior uveal melanoma regulation of tumor development through mitf, bcl2 and cyclin d2作用的微rna - 182通过mitf后葡萄膜黑色素瘤肿瘤发展的监管,bcl2和细胞周期蛋白d2.pdfVIP

Role of MicroRNA-182 in Posterior Uveal Melanoma: Regulation of Tumor Development through MITF, BCL2 and Cyclin D2 1,2 3 1,2 1,2 1,2 1,2 Dongsheng Yan *, Xiang Da Dong , Xiaoyan Chen , Shasha Yao , Lihua Wang , Jiao Wang , Chao Wang1,2, Dan-Ning Hu2,4, Jia Qu1,2, LiLi Tu1,2* 1 School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang, China, 2 State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of the People’s Republic of China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China, 3 Department of Surgery, Stamford Hospital – Affiliate of Columbia University, Stamford, Connecticut, United States of America, 4 Tissue Culture Center, New York Eye and Ear Infirmary, New York Medical College, New York, New York, United States of America Abstract MicroRNAs (miRNAs) are endogenous small non-coding RNAs that play central roles in diverse pathological processes. In this study, we investigated the effect of microRNA-182 (miR-182) on the development of posterior uveal melanomas. Initially, we demonstrated that miR-182 expression was dependent on p53 induction in uveal melanoma cells. Interestingly, transient transfection of miR-182 into cultured uveal melanoma cells led to a significant decrease in cell growth, migration, and invasiveness. Cells transfected with miR-182 demonstrated cell cycle G1 arrest and increased apoptotic activity. Using bioinformatics, we identified three potential targets of miR-182, namely MITF, BCL2 and cyclin D2. miR-182 was shown to have activity on mRNA expression by targeting the 39 untranslated region of MITF, BCL