MicroRNA-137 Targets Carboxyl-terminal Binding Protein 1 in Melanoma Cell Lines

<p>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...

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Main Author: Yu Deng, Hui Deng, Feng Bi, Jing Liu, Lynn T. Bemis, David Norris, Xiao-Jing Wang, Qinghong Zhang
Format: Article
Language:English
Published: Ivyspring International Publisher 2011-01-01
Series:International Journal of Biological Sciences
Online Access:http://www.biolsci.org/v07p0133.htm
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author Yu Deng, Hui Deng, Feng Bi, Jing Liu, Lynn T. Bemis, David Norris, Xiao-Jing Wang, Qinghong Zhang
author_facet Yu Deng, Hui Deng, Feng Bi, Jing Liu, Lynn T. Bemis, David Norris, Xiao-Jing Wang, Qinghong Zhang
author_sort Yu Deng, Hui Deng, Feng Bi, Jing Liu, Lynn T. Bemis, David Norris, Xiao-Jing Wang, Qinghong Zhang
collection DOAJ
description <p>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&#8242; untranslated region (3&#8242;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.</p>
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spelling doaj.art-b1334acdd76e4c269af12a576e9eb4822022-12-22T01:16:14ZengIvyspring International PublisherInternational Journal of Biological Sciences1449-22882011-01-0171133137MicroRNA-137 Targets Carboxyl-terminal Binding Protein 1 in Melanoma Cell LinesYu Deng, Hui Deng, Feng Bi, Jing Liu, Lynn T. Bemis, David Norris, Xiao-Jing Wang, Qinghong Zhang<p>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&#8242; untranslated region (3&#8242;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.</p>http://www.biolsci.org/v07p0133.htm
spellingShingle Yu Deng, Hui Deng, Feng Bi, Jing Liu, Lynn T. Bemis, David Norris, Xiao-Jing Wang, Qinghong Zhang
MicroRNA-137 Targets Carboxyl-terminal Binding Protein 1 in Melanoma Cell Lines
International Journal of Biological Sciences
title MicroRNA-137 Targets Carboxyl-terminal Binding Protein 1 in Melanoma Cell Lines
title_full MicroRNA-137 Targets Carboxyl-terminal Binding Protein 1 in Melanoma Cell Lines
title_fullStr MicroRNA-137 Targets Carboxyl-terminal Binding Protein 1 in Melanoma Cell Lines
title_full_unstemmed MicroRNA-137 Targets Carboxyl-terminal Binding Protein 1 in Melanoma Cell Lines
title_short MicroRNA-137 Targets Carboxyl-terminal Binding Protein 1 in Melanoma Cell Lines
title_sort microrna 137 targets carboxyl terminal binding protein 1 in melanoma cell lines
url http://www.biolsci.org/v07p0133.htm
work_keys_str_mv AT yudenghuidengfengbijingliulynntbemisdavidnorrisxiaojingwangqinghongzhang microrna137targetscarboxylterminalbindingprotein1inmelanomacelllines