Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma.
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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肿瘤抑制因子 PDCD4 调节 miR-184 介导的 C-MYC 和 BCL2 直接抑制，从而阻断鼻咽癌细胞的生长和存活。
DOI：
10.1038/cddis.2013.376
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发表时间：
2013-10-24
影响因子：
9
通讯作者：
Fang, Weiyi
中科院分区：
文献类型：
--
作者：
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
程序性细胞死亡4(PDCD4)是一种新型的肿瘤抑制因子，可抑制肿瘤细胞的增殖、迁移和侵袭，促进肿瘤细胞的凋亡。然而，在包括鼻咽癌(NPC)在内的肿瘤中，其抑瘤作用的分子机制尚不清楚。在这项研究中，PDCD4表达下调与鼻咽癌的进展状况和不良预后显著相关。PDCD4通过调控C-MYC调控的细胞周期、bcl2介导的线粒体凋亡抵抗信号和癌基因转录因子C-jun，显著抑制鼻咽癌细胞的增殖和存活能力。此外，由PDCD4直接针对BCL2和C-MYC调控的抑瘤miRNA miR-184参与了PDCD4介导的对鼻咽癌细胞增殖和存活的抑制作用。此外，我们还发现PDCD4通过PI3K/AKT/JNK/C-Jun途径减少C-Jun与miR-184启动子区域AP-1元件的结合，并刺激miR-184的表达。在临床新鲜标本中，鼻咽癌组织中PDCD4mRNA水平降低与miR-184表达呈正相关。我们的研究首次证明，PDCD4作为肿瘤抑制因子，通过PI3K/AKT和JNK/C-Jun途径调节miR-184介导的BCL2和C-MYC直接靶向抑制鼻咽癌细胞的增殖和存活。
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.
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影响因子：
9
作者：
通讯作者：
--
DOI：
10.1016/s0006-291x(02)02129-0
发表时间：
2002-09-13
影响因子：
3.1
作者：
Göke, A;Göke, R;Chen, YHH
通讯作者：
Chen, YHH
影响因子：
6.4
作者：
Wang, Shuang;Fang, Weiyi
通讯作者：
Fang, Weiyi
影响因子：
8
作者：
Bitomsky, N;Böhm, M;Klempnauer, KH
通讯作者：
Klempnauer, KH
DOI：
10.1007/s00432-011-1140-8
发表时间：
2012-04-01
影响因子：
3.6
作者：
Cao, Zhang;Yoon, Jung Hwan;Park, Won Sang
通讯作者：
Park, Won Sang