Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma

Programmed cell death 4 (PDCD4), a novel tumor suppressor, inhibits cell proliferation, migration and invasion as well as promotes cell apoptosis in tumors. However, the molecular mechanism of its tumor-suppressive function remains largely unknown in tumors including nasopharyngeal carcinoma (NPC)....

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Main Authors:	Zhen, Yan, Liu, Zhen, Yang, Huiling, Yu, Xiaoli, Wu, Qiangyun, Hua, Shengni, Long, Xiaobin, Jiang, Qingping, Song, Ye, Cheng, Chao, Wang, Hao, Zhao, Menyang, Fu, Qiaofen, Lyu, Xiaoming, Chen, Yiyu, Fan, Yue, Liu, Yan, Li, Xin, Fang, Weiyi
Format:	Online
Language:	English
Published:	Nature Publishing Group 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824685/

id	pubmed-3824685
recordtype	oai_dc
spelling	pubmed-38246852013-11-12 Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma Zhen, Yan Liu, Zhen Yang, Huiling Yu, Xiaoli Wu, Qiangyun Hua, Shengni Long, Xiaobin Jiang, Qingping Song, Ye Cheng, Chao Wang, Hao Zhao, Menyang Fu, Qiaofen Lyu, Xiaoming Chen, Yiyu Fan, Yue Liu, Yan Li, Xin Fang, Weiyi Original Article Programmed cell death 4 (PDCD4), a novel tumor suppressor, inhibits cell proliferation, migration and invasion as well as promotes cell apoptosis in tumors. However, the molecular mechanism of its tumor-suppressive function remains largely unknown in tumors including nasopharyngeal carcinoma (NPC). In this study, downregulated PDCD4 expression was significantly associated with the status of NPC progression and poor prognosis. PDCD4 markedly suppressed the ability of cell proliferation and cell survival by modulating C-MYC-controlled cell cycle and BCL-2-mediated mitochondrion apoptosis resistance signals, and oncogenic transcription factor C-JUN in NPC. Furthermore, miR-184, a tumor-suppressive miRNA modulated by PDCD4 directly targeting BCL2 and C-MYC, participated in PDCD4-mediated suppression of cell proliferation and survival in NPC. Further, we found that PDCD4 decreased the binding of C-Jun to the AP-1 element on the miR-184 promoter regions by PI3K/AKT/JNK/C-Jun pathway and stimulated miR-184 expression. In clinical fresh specimens, reduced PDCD4 mRNA level was positively correlated with miR-184 expression in NPC. Our studies are the first to demonstrate that PDCD4 as tumor suppressor regulated miR-184-mediated direct targeting of BCL2 and C-MYC via PI3K/AKT and JNK/C-Jun pathway attenuating cell proliferation and survival in NPC. Nature Publishing Group 2013-10 2013-10-24 /pmc/articles/PMC3824685/ /pubmed/24157866 http://dx.doi.org/10.1038/cddis.2013.376 Text en Copyright © 2013 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhen, Yan Liu, Zhen Yang, Huiling Yu, Xiaoli Wu, Qiangyun Hua, Shengni Long, Xiaobin Jiang, Qingping Song, Ye Cheng, Chao Wang, Hao Zhao, Menyang Fu, Qiaofen Lyu, Xiaoming Chen, Yiyu Fan, Yue Liu, Yan Li, Xin Fang, Weiyi
spellingShingle	Zhen, Yan Liu, Zhen Yang, Huiling Yu, Xiaoli Wu, Qiangyun Hua, Shengni Long, Xiaobin Jiang, Qingping Song, Ye Cheng, Chao Wang, Hao Zhao, Menyang Fu, Qiaofen Lyu, Xiaoming Chen, Yiyu Fan, Yue Liu, Yan Li, Xin Fang, Weiyi Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma
author_facet	Zhen, Yan Liu, Zhen Yang, Huiling Yu, Xiaoli Wu, Qiangyun Hua, Shengni Long, Xiaobin Jiang, Qingping Song, Ye Cheng, Chao Wang, Hao Zhao, Menyang Fu, Qiaofen Lyu, Xiaoming Chen, Yiyu Fan, Yue Liu, Yan Li, Xin Fang, Weiyi
author_sort	Zhen, Yan
title	Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma
title_short	Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma
title_full	Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma
title_fullStr	Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma
title_full_unstemmed	Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma
title_sort	tumor suppressor pdcd4 modulates mir-184-mediated direct suppression of c-myc and bcl2 blocking cell growth and survival in nasopharyngeal carcinoma
description	Programmed cell death 4 (PDCD4), a novel tumor suppressor, inhibits cell proliferation, migration and invasion as well as promotes cell apoptosis in tumors. However, the molecular mechanism of its tumor-suppressive function remains largely unknown in tumors including nasopharyngeal carcinoma (NPC). In this study, downregulated PDCD4 expression was significantly associated with the status of NPC progression and poor prognosis. PDCD4 markedly suppressed the ability of cell proliferation and cell survival by modulating C-MYC-controlled cell cycle and BCL-2-mediated mitochondrion apoptosis resistance signals, and oncogenic transcription factor C-JUN in NPC. Furthermore, miR-184, a tumor-suppressive miRNA modulated by PDCD4 directly targeting BCL2 and C-MYC, participated in PDCD4-mediated suppression of cell proliferation and survival in NPC. Further, we found that PDCD4 decreased the binding of C-Jun to the AP-1 element on the miR-184 promoter regions by PI3K/AKT/JNK/C-Jun pathway and stimulated miR-184 expression. In clinical fresh specimens, reduced PDCD4 mRNA level was positively correlated with miR-184 expression in NPC. Our studies are the first to demonstrate that PDCD4 as tumor suppressor regulated miR-184-mediated direct targeting of BCL2 and C-MYC via PI3K/AKT and JNK/C-Jun pathway attenuating cell proliferation and survival in NPC.
publisher	Nature Publishing Group
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824685/
_version_	1612025777637818368

Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma

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