Cargando…

Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer

As one of the most aggressive types of tumor, pancreatic cancer is a principal cause of tumor-associated mortality. Negative associations between microRNA-29 (miR-29) and DNA methyltransferases (DNMT) 3a and 3b have been demonstrated to be associated with the carcinogenesis of a number of types of c...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Li-Hua, Huang, Ju, Wu, Cheng-Rong, Huang, Liu-Ye, Cui, Jun, Xing, Zhi-Zhi, Zhao, Chun-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783451/
https://www.ncbi.nlm.nih.gov/pubmed/29207141
http://dx.doi.org/10.3892/mmr.2017.8145
_version_ 1783295280437788672
author Wang, Li-Hua
Huang, Ju
Wu, Cheng-Rong
Huang, Liu-Ye
Cui, Jun
Xing, Zhi-Zhi
Zhao, Chun-Yu
author_facet Wang, Li-Hua
Huang, Ju
Wu, Cheng-Rong
Huang, Liu-Ye
Cui, Jun
Xing, Zhi-Zhi
Zhao, Chun-Yu
author_sort Wang, Li-Hua
collection PubMed
description As one of the most aggressive types of tumor, pancreatic cancer is a principal cause of tumor-associated mortality. Negative associations between microRNA-29 (miR-29) and DNA methyltransferases (DNMT) 3a and 3b have been demonstrated to be associated with the carcinogenesis of a number of types of cancer; however, this has not been completely elucidated in pancreatic cancer. In the present study, pancreatic cancer tissues (n=15) and corresponding paracancerous tissues (n=15) were obtained and the results of reverse transcription-quantitative polymerase chain reaction analysis indicated decreased expression of miR-29b and enhanced mRNA expression of DNMT3b in pancreatic cancer tissues, compared with the corresponding paracancerous tissues. Increased protein expression of DNMT3b was demonstrated by western blotting and immunohistochemistry. In addition, the negative association between miR-29b and DNMT3b was noted in pancreatic cancer tissues, and luciferase reporter assays confirmed that miR-29b was able to directly target DNMT3b in vitro. Notably, miR-29b overexpression was able to decrease cell viability and to promote the apoptosis by targeting DNMT3b, and the knockdown of DNMT3b exhibited consistent results in vitro and in vivo. The results of the present study suggested that miR-29b, as a tumor suppressor, may be a novel target for the development of treatments for pancreatic cancer.
format Online
Article
Text
id pubmed-5783451
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-57834512018-02-05 Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer Wang, Li-Hua Huang, Ju Wu, Cheng-Rong Huang, Liu-Ye Cui, Jun Xing, Zhi-Zhi Zhao, Chun-Yu Mol Med Rep Articles As one of the most aggressive types of tumor, pancreatic cancer is a principal cause of tumor-associated mortality. Negative associations between microRNA-29 (miR-29) and DNA methyltransferases (DNMT) 3a and 3b have been demonstrated to be associated with the carcinogenesis of a number of types of cancer; however, this has not been completely elucidated in pancreatic cancer. In the present study, pancreatic cancer tissues (n=15) and corresponding paracancerous tissues (n=15) were obtained and the results of reverse transcription-quantitative polymerase chain reaction analysis indicated decreased expression of miR-29b and enhanced mRNA expression of DNMT3b in pancreatic cancer tissues, compared with the corresponding paracancerous tissues. Increased protein expression of DNMT3b was demonstrated by western blotting and immunohistochemistry. In addition, the negative association between miR-29b and DNMT3b was noted in pancreatic cancer tissues, and luciferase reporter assays confirmed that miR-29b was able to directly target DNMT3b in vitro. Notably, miR-29b overexpression was able to decrease cell viability and to promote the apoptosis by targeting DNMT3b, and the knockdown of DNMT3b exhibited consistent results in vitro and in vivo. The results of the present study suggested that miR-29b, as a tumor suppressor, may be a novel target for the development of treatments for pancreatic cancer. D.A. Spandidos 2018-02 2017-11-23 /pmc/articles/PMC5783451/ /pubmed/29207141 http://dx.doi.org/10.3892/mmr.2017.8145 Text en Copyright: © Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Wang, Li-Hua
Huang, Ju
Wu, Cheng-Rong
Huang, Liu-Ye
Cui, Jun
Xing, Zhi-Zhi
Zhao, Chun-Yu
Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer
title Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer
title_full Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer
title_fullStr Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer
title_full_unstemmed Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer
title_short Downregulation of miR-29b targets DNMT3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer
title_sort downregulation of mir-29b targets dnmt3b to suppress cellular apoptosis and enhance proliferation in pancreatic cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783451/
https://www.ncbi.nlm.nih.gov/pubmed/29207141
http://dx.doi.org/10.3892/mmr.2017.8145
work_keys_str_mv AT wanglihua downregulationofmir29btargetsdnmt3btosuppresscellularapoptosisandenhanceproliferationinpancreaticcancer
AT huangju downregulationofmir29btargetsdnmt3btosuppresscellularapoptosisandenhanceproliferationinpancreaticcancer
AT wuchengrong downregulationofmir29btargetsdnmt3btosuppresscellularapoptosisandenhanceproliferationinpancreaticcancer
AT huangliuye downregulationofmir29btargetsdnmt3btosuppresscellularapoptosisandenhanceproliferationinpancreaticcancer
AT cuijun downregulationofmir29btargetsdnmt3btosuppresscellularapoptosisandenhanceproliferationinpancreaticcancer
AT xingzhizhi downregulationofmir29btargetsdnmt3btosuppresscellularapoptosisandenhanceproliferationinpancreaticcancer
AT zhaochunyu downregulationofmir29btargetsdnmt3btosuppresscellularapoptosisandenhanceproliferationinpancreaticcancer