PMID- 27936052 OWN - NLM STAT- MEDLINE DCOM- 20170707 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 11 IP - 12 DP - 2016 TI - MicroRNA-182 Suppresses HGF/SF-Induced Increases in Retinal Pigment Epithelial Cell Proliferation and Migration through Targeting c-Met. PG - e0167684 LID - 10.1371/journal.pone.0167684 [doi] LID - e0167684 AB - As increases in hepatocyte growth factor/scatter factor (HGF/SF) induce retinal pigment epithelial (RPE) migration and proliferation into the vitreous cavity and contribute to proliferative vitreoretinopathy (PVR) development, we determined if changes in miR-182 expression affect such behavioral changes. We found that miR-182 expression was less in PVR clinical samples than in primary RPE cells whereas c-Met was upregulated. Ectopic miR-182 inhibited RPE cell proliferation, cell cycle, and migration. Bioinformatic analysis identified c-Met as a miR-182 target, which was confirmed with the luciferase reporter assay. Transfection of miR-182 into RPE cells induced c-Met downregulation, which led to reduced cell proliferation and migration through declines in p-Akt formation. MiR-182 downregulation along with c-Met upregulation in PVR tissues suggest that these two opposing effects play important roles in PVR development. As ectopic miR-182 expression suppressed RPE cell proliferation and migration, strategies to selectively upregulate miR-182 expression in a clinical setting may provide a novel option to treat this disease. FAU - Wang, Lihua AU - Wang L AD - School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - 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. FAU - Dong, Feng AU - Dong F AD - The First Affiliated Hospital of College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Reinach, Peter S AU - Reinach PS AD - School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - 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. FAU - He, Dandan AU - He D AD - School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - 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. FAU - Zhao, Xiaoting AU - Zhao X AD - School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - 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. FAU - Chen, Xiaoyan AU - Chen X AD - School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - 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. FAU - Hu, Dan-Ning AU - Hu DN AD - 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. AD - Tissue Culture Center, the New York Eye and Ear Infirmary, New York Medical College, New York, New York, United States of America. FAU - Yan, Dongsheng AU - Yan D AUID- ORCID: 0000-0003-0551-2219 AD - School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. AD - 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. LA - eng PT - Journal Article DEP - 20161209 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (HGF protein, human) RN - 0 (MicroRNAs) RN - 0 (Mirn182 microRNA, human) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) SB - IM MH - Adult MH - Cell Movement MH - *Cell Proliferation MH - Cells, Cultured MH - Down-Regulation MH - *Gene Expression Regulation MH - Hepatocyte Growth Factor/*metabolism MH - Humans MH - MicroRNAs/*genetics MH - Proto-Oncogene Proteins c-met/*genetics MH - Retinal Pigment Epithelium/cytology/metabolism/*pathology MH - Up-Regulation MH - Vitreoretinopathy, Proliferative/*genetics/metabolism/pathology PMC - PMC5147940 COIS- The authors have declared that no competing interests exist. EDAT- 2016/12/10 06:00 MHDA- 2017/07/08 06:00 PMCR- 2016/12/09 CRDT- 2016/12/10 06:00 PHST- 2016/01/18 00:00 [received] PHST- 2016/11/18 00:00 [accepted] PHST- 2016/12/10 06:00 [entrez] PHST- 2016/12/10 06:00 [pubmed] PHST- 2017/07/08 06:00 [medline] PHST- 2016/12/09 00:00 [pmc-release] AID - PONE-D-16-02329 [pii] AID - 10.1371/journal.pone.0167684 [doi] PST - epublish SO - PLoS One. 2016 Dec 9;11(12):e0167684. doi: 10.1371/journal.pone.0167684. eCollection 2016.