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TSA Suppresses miR-106b-93-25 Cluster Expression through Downregulation of MYC and Inhibits Proliferation and Induces Apoptosis in Human EMC

Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti-tumor agents and have manifested the ability to decrease proliferation and increase apoptosis in different cancer cells. A significant number of genes have been identified as potential effectors responsible for the anti-tumo...

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Autores principales: Zhao, Zhi-Ning, Bai, Jiu-Xu, Zhou, Qiang, Yan, Bo, Qin, Wei-Wei, Jia, Lin-Tao, Meng, Yan-Ling, Jin, Bo-Quan, Yao, Li-Bo, Wang, Tao, Yang, An-Gang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446970/
https://www.ncbi.nlm.nih.gov/pubmed/23028803
http://dx.doi.org/10.1371/journal.pone.0045133
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author Zhao, Zhi-Ning
Bai, Jiu-Xu
Zhou, Qiang
Yan, Bo
Qin, Wei-Wei
Jia, Lin-Tao
Meng, Yan-Ling
Jin, Bo-Quan
Yao, Li-Bo
Wang, Tao
Yang, An-Gang
author_facet Zhao, Zhi-Ning
Bai, Jiu-Xu
Zhou, Qiang
Yan, Bo
Qin, Wei-Wei
Jia, Lin-Tao
Meng, Yan-Ling
Jin, Bo-Quan
Yao, Li-Bo
Wang, Tao
Yang, An-Gang
author_sort Zhao, Zhi-Ning
collection PubMed
description Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti-tumor agents and have manifested the ability to decrease proliferation and increase apoptosis in different cancer cells. A significant number of genes have been identified as potential effectors responsible for the anti-tumor function of HDAC inhibitor. However, the molecular mechanisms of these HDAC inhibitors in this process remain largely undefined. In the current study, we searched for microRNAs (miRs) that were affected by HDAC inhibitor trichostatin (TSA) and investigated their effects in endometrial cancer (EMC) cells. Our data showed that TSA significantly inhibited the growth of EMC cells and induced their apoptosis. Among the miRNAs that altered in the presence of TSA, the miR-106b-93-25 cluster, together with its host gene MCM7, were obviously down-regulated in EMC cells. p21 and BIM, which were identified as target genes of miR-106b-93-25 cluster, increased in TSA treated tumor cells and were responsible for cell cycle arrest and apoptosis. We further identified MYC as a regulator of miR-106b-93-25 cluster and demonstrated its down-regulation in the presence of TSA resulted in the reduction of miR-106b-93-25 cluster and up-regulation of p21 and BIM. More important, we found miR-106b-93-25 cluster was up-regulated in clinical EMC samples in association with the overexpression of MCM7 and MYC and the down-regulation of p21 and BIM. Thus our studies strongly indicated TSA inhibited EMC cell growth and induced cell apoptosis and cell cycle arrest at least partially through the down-regulation of the miR-106b-93-25 cluster and up-regulation of it's target genes p21 and BIM via MYC.
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spelling pubmed-34469702012-10-01 TSA Suppresses miR-106b-93-25 Cluster Expression through Downregulation of MYC and Inhibits Proliferation and Induces Apoptosis in Human EMC Zhao, Zhi-Ning Bai, Jiu-Xu Zhou, Qiang Yan, Bo Qin, Wei-Wei Jia, Lin-Tao Meng, Yan-Ling Jin, Bo-Quan Yao, Li-Bo Wang, Tao Yang, An-Gang PLoS One Research Article Histone deacetylase (HDAC) inhibitors are emerging as a novel class of anti-tumor agents and have manifested the ability to decrease proliferation and increase apoptosis in different cancer cells. A significant number of genes have been identified as potential effectors responsible for the anti-tumor function of HDAC inhibitor. However, the molecular mechanisms of these HDAC inhibitors in this process remain largely undefined. In the current study, we searched for microRNAs (miRs) that were affected by HDAC inhibitor trichostatin (TSA) and investigated their effects in endometrial cancer (EMC) cells. Our data showed that TSA significantly inhibited the growth of EMC cells and induced their apoptosis. Among the miRNAs that altered in the presence of TSA, the miR-106b-93-25 cluster, together with its host gene MCM7, were obviously down-regulated in EMC cells. p21 and BIM, which were identified as target genes of miR-106b-93-25 cluster, increased in TSA treated tumor cells and were responsible for cell cycle arrest and apoptosis. We further identified MYC as a regulator of miR-106b-93-25 cluster and demonstrated its down-regulation in the presence of TSA resulted in the reduction of miR-106b-93-25 cluster and up-regulation of p21 and BIM. More important, we found miR-106b-93-25 cluster was up-regulated in clinical EMC samples in association with the overexpression of MCM7 and MYC and the down-regulation of p21 and BIM. Thus our studies strongly indicated TSA inhibited EMC cell growth and induced cell apoptosis and cell cycle arrest at least partially through the down-regulation of the miR-106b-93-25 cluster and up-regulation of it's target genes p21 and BIM via MYC. Public Library of Science 2012-09-19 /pmc/articles/PMC3446970/ /pubmed/23028803 http://dx.doi.org/10.1371/journal.pone.0045133 Text en © 2012 Zhao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhao, Zhi-Ning
Bai, Jiu-Xu
Zhou, Qiang
Yan, Bo
Qin, Wei-Wei
Jia, Lin-Tao
Meng, Yan-Ling
Jin, Bo-Quan
Yao, Li-Bo
Wang, Tao
Yang, An-Gang
TSA Suppresses miR-106b-93-25 Cluster Expression through Downregulation of MYC and Inhibits Proliferation and Induces Apoptosis in Human EMC
title TSA Suppresses miR-106b-93-25 Cluster Expression through Downregulation of MYC and Inhibits Proliferation and Induces Apoptosis in Human EMC
title_full TSA Suppresses miR-106b-93-25 Cluster Expression through Downregulation of MYC and Inhibits Proliferation and Induces Apoptosis in Human EMC
title_fullStr TSA Suppresses miR-106b-93-25 Cluster Expression through Downregulation of MYC and Inhibits Proliferation and Induces Apoptosis in Human EMC
title_full_unstemmed TSA Suppresses miR-106b-93-25 Cluster Expression through Downregulation of MYC and Inhibits Proliferation and Induces Apoptosis in Human EMC
title_short TSA Suppresses miR-106b-93-25 Cluster Expression through Downregulation of MYC and Inhibits Proliferation and Induces Apoptosis in Human EMC
title_sort tsa suppresses mir-106b-93-25 cluster expression through downregulation of myc and inhibits proliferation and induces apoptosis in human emc
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3446970/
https://www.ncbi.nlm.nih.gov/pubmed/23028803
http://dx.doi.org/10.1371/journal.pone.0045133
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