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miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma

Programmed cell death 4 (PDCD4), as a tumor suppressor gene, is frequently reduced in a variety of tumors, including gastric cancer. Previous findings have indicated that PDCD4 participates in tumorigenesis through the regulation of apoptosis, but the molecular basis of this process has not been ful...

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Autores principales: Liang, Hongwei, Wang, Feng, Chu, Danping, Zhang, Weijie, Liao, Zhicong, Fu, Zheng, Yan, Xin, Zhu, Hao, Guo, Wen, Zhang, Yujing, Guan, Wenxian, Chen, Xi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810498/
https://www.ncbi.nlm.nih.gov/pubmed/27021515
http://dx.doi.org/10.1038/srep23772
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author Liang, Hongwei
Wang, Feng
Chu, Danping
Zhang, Weijie
Liao, Zhicong
Fu, Zheng
Yan, Xin
Zhu, Hao
Guo, Wen
Zhang, Yujing
Guan, Wenxian
Chen, Xi
author_facet Liang, Hongwei
Wang, Feng
Chu, Danping
Zhang, Weijie
Liao, Zhicong
Fu, Zheng
Yan, Xin
Zhu, Hao
Guo, Wen
Zhang, Yujing
Guan, Wenxian
Chen, Xi
author_sort Liang, Hongwei
collection PubMed
description Programmed cell death 4 (PDCD4), as a tumor suppressor gene, is frequently reduced in a variety of tumors, including gastric cancer. Previous findings have indicated that PDCD4 participates in tumorigenesis through the regulation of apoptosis, but the molecular basis of this process has not been fully elucidated, and no studies have shown the upstream regulation of this gene in gastric cancer. In this study, we used bioinformatics analysis to search for miRNAs that could potentially target PDCD4 and identified miR-93 as a candidate. Moreover, we observed the inverse correlation between miR-93 and PDCD4 protein levels, but not mRNA levels, in human gastric cancer tissues. We further experimentally validated PDCD4 as the direct target of miR-93 by evaluating PDCD4 expression in gastric cancer cells after the overexpression or knockdown of miR-93. Additionally, the biological consequences of targeting PDCD4 through miR-93 were examined using cell apoptosis assays in vitro. We demonstrated that the repression of PDCD4 through miR-93 suppressed the apoptosis of gastric cancer cells. Finally, we revealed that miR-93 promoted the development of gastric tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, the findings of the present study indicated the oncogenic role of miR-93 in gastric cancer tumorigenesis through targeting PDCD4, particularly in apoptosis.
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spelling pubmed-48104982016-04-04 miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma Liang, Hongwei Wang, Feng Chu, Danping Zhang, Weijie Liao, Zhicong Fu, Zheng Yan, Xin Zhu, Hao Guo, Wen Zhang, Yujing Guan, Wenxian Chen, Xi Sci Rep Article Programmed cell death 4 (PDCD4), as a tumor suppressor gene, is frequently reduced in a variety of tumors, including gastric cancer. Previous findings have indicated that PDCD4 participates in tumorigenesis through the regulation of apoptosis, but the molecular basis of this process has not been fully elucidated, and no studies have shown the upstream regulation of this gene in gastric cancer. In this study, we used bioinformatics analysis to search for miRNAs that could potentially target PDCD4 and identified miR-93 as a candidate. Moreover, we observed the inverse correlation between miR-93 and PDCD4 protein levels, but not mRNA levels, in human gastric cancer tissues. We further experimentally validated PDCD4 as the direct target of miR-93 by evaluating PDCD4 expression in gastric cancer cells after the overexpression or knockdown of miR-93. Additionally, the biological consequences of targeting PDCD4 through miR-93 were examined using cell apoptosis assays in vitro. We demonstrated that the repression of PDCD4 through miR-93 suppressed the apoptosis of gastric cancer cells. Finally, we revealed that miR-93 promoted the development of gastric tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, the findings of the present study indicated the oncogenic role of miR-93 in gastric cancer tumorigenesis through targeting PDCD4, particularly in apoptosis. Nature Publishing Group 2016-03-29 /pmc/articles/PMC4810498/ /pubmed/27021515 http://dx.doi.org/10.1038/srep23772 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Liang, Hongwei
Wang, Feng
Chu, Danping
Zhang, Weijie
Liao, Zhicong
Fu, Zheng
Yan, Xin
Zhu, Hao
Guo, Wen
Zhang, Yujing
Guan, Wenxian
Chen, Xi
miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma
title miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma
title_full miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma
title_fullStr miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma
title_full_unstemmed miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma
title_short miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma
title_sort mir-93 functions as an oncomir for the downregulation of pdcd4 in gastric carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810498/
https://www.ncbi.nlm.nih.gov/pubmed/27021515
http://dx.doi.org/10.1038/srep23772
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