title: MicroRNA-206: Effective Inhibition of Gastric Cancer Progression through the c-Met Pathway.
abstract: MicroRNAs are endogenous short chain nucleotide RNAs that regulate gene function by direct binding of target mRNAs. In this study, we investigated the effects of microRNA-206 (miR-206) on the development of gastric cancer. miR-206 was first confirmed to be downregulated in gastric cancer specimens. Conversely, upregulation of c-Met was confirmed in tissue samples of human gastric cancer, with its level inversely correlated with miR-206 expression. Introduction of miR-206 inhibited cellular proliferation by inducing G1 cell cycle arrest, as well as migration and invasion. Moreover, important proliferation and/or migration related molecules such as c-Met, CDK4, p-Rb, p-Akt and p-ERK were confirmed to be downregulated by Western blot analysis. Targeting of c-Met also directly affected AGS cell proliferation, migration and invasion. In vivo, miR-206 expressing tumor cells also displayed growth delay in comparison to unaffected tumor cells. Our results demonstrated that miR-206 suppressed c-Met expression in gastric cancer and could function as a potent tumor suppressor in c-Met overexpressing tumors. Inhibition of miR-206 function could contribute to aberrant cell proliferation and migration, leading to gastric cancer development.
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of P. R. China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yan
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of P. R. China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang, China; The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of P. R. China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
authors.forename: Guangjing
authors.initials: G
authors.lastname: Li
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of P. R. China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
authors.forename: Linglin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of P. R. China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Wenzhou Medical University, Wenzhou, Zhejiang, China; School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China; State Key Laboratory Cultivation Base and Key Laboratory of Vision Science, Ministry of Health of P. R. China, Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, Zhejiang, China.
authors.forename: LiLi
authors.initials: L
authors.lastname: Tu
authors.affiliation: Department of Surgery, Stamford Hospital-Affiliate of Columbia University, Stamford, Connecticut, United States of America.
authors.forename: Xiang Da
authors.initials: XD
authors.lastname: Dong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D047368:Tumor Burden
chemical_list: C546087:MIRN206 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3