title: MicroRNA-137 targets carboxyl-terminal binding protein 1 in melanoma cell lines.
abstract: Carboxyl-terminal binding protein 1 (CtBP1) is a transcriptional co-repressor that represses expression of various tumor suppressor genes. In the present study, we identified miR-137 as a potential regulator of CtBP1 expression in melanoma cells. Expression of miR-137 in melanoma cell lines was found to inversely correlate with CtBP1 levels. Target Scan predicted a putative site for miR-137 within the CtBP1 3' untranslated region (3'UTR) at nt 710-716, which is highly conserved across species. To explore the mechanism of miR-137 targeting CtBP1, we performed an Argonaute 2 (Ago2)-pull down assay, and miR-137 was identified in complex with CtBP1 mRNA. miR-137 suppressed CtBP1 3' UTR luciferase-reporter activity, and this effect was lost with deletion of the putative 3' UTR target-site. Consistent with the results of the reporter assay, ectopic expression of miR-137 reduced expression levels of CtBP1. Furthermore, expression of miR-137 increased the immediate downstream effectors of CtBP1, such as E-cadherin and Bax. The human miR-137 gene is located at chromosome 1p22, which has previously been determined to be a susceptive region for melanoma. This study suggests miR-137 may act as a tumor suppressor by directly targeting CtBP1 to inhibit epithelial-mesenchymal transition (EMT) and inducing apoptosis of melanoma cells, thus illustrating a functional link between miR-137 and CtBP1 in melanoma development.
authors.affiliation: Laboratory of Signal Transduction & Molecular Targeted Therapy, State Key Laboratory of Biotherapy/ Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, Sichuan Province 610041, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.forename: Feng
authors.initials: F
authors.lastname: Bi
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Lynn T
authors.initials: LT
authors.lastname: Bemis
authors.forename: David
authors.initials: D
authors.lastname: Norris
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Wang
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D060565:Argonaute Proteins; D001665:Binding Sites; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; C494826:BAX protein, human; D015820:Cadherins; D004268:DNA-Binding Proteins; D015852:Eukaryotic Initiation Factor-2; C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein