Loss of connective tissue growth factor as an unfavorable prognosis factor activates miR-18b by PI3K/AKT/C-Jun and C-Myc and promotes cell growth in nasopharyngeal carcinoma.
Loss of connective tissue growth factor as an unfavorable prognosis factor activates miR-18b by PI3K/AKT/C-Jun and C-Myc and promotes cell growth in nasopharyngeal carcinoma.
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DOI：
10.1038/cddis.2013.153
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发表时间：
2013-05-16
影响因子：
9
通讯作者：
Fang, W.
中科院分区：
文献类型：
--
作者：
Yu, X.;Zhen, Y.;Yang, H.;Wang, H.;Zhou, Y.;Wang, E.;Marincola, F. M.;Mai, C.;Chen, Y.;Wei, H.;Song, Y.;Lyu, X.;Ye, Y.;Cai, L.;Wu, Q.;Zhao, M.;Hua, S.;Fu, Q.;Zhang, Y.;Yao, K.;Liu, Z.;Li, X.;Fang, W.
结缔组织生长因子（CTGF）在不同类型的癌症中具有不同的作用。然而，CTGF在人鼻咽癌（NPC）肿瘤进展和预后中的参与及其分子基础几乎从未报道。在这项研究中，我们观察到 CTGF 表达下调与 NPC 进展和不良预后显着相关。 CTGF的敲低显着提高了体内和体外细胞增殖的能力。随后，我们发现 CTGF 的减少增加了 miR-18b 的表达，miR-18b 是一种促进细胞增殖的 Oncomir。此外，我们发现CTGF介导的miR-18b上调减弱依赖于转录因子Jun原癌基因（C-Jun）和v-Myc骨髓细胞瘤病病毒癌基因同源物（C-Myc）通过磷酸肌醇3激酶（PI3K）/AKT途径与miR-18b启动子区的结合增加。最后，我们进一步发现miR-18b直接抑制鼻咽癌中CTGF的表达。在临床新鲜标本中，miR-18b广泛过表达，并与鼻咽癌中CTGF表达呈负相关。我们的研究首次证明，CTGF 减少是一种不利的预后因素，可通过 PI3K/AKT/C-Jun 和 C-Myc 介导 miR-18b（一种 Oncomir 直接抑制 CTGF 表达）的激活，并促进 NPC 细胞生长。
Connective tissue growth factor (CTGF) has different roles in different types of cancer. However, the involvement and molecular basis of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC) have almost never been reported. In this study, we observed that downregulated CTGF expression was significantly associated with NPC progression and poor prognosis. Knockdown of CTGF markedly elevated the ability of cell proliferation in vivo and in vitro. Subsequently, we discovered that the reduction of CTGF increased the expression of miR-18b, an oncomir-promoting cell proliferation. Further, we discovered that attenuated CTGF-mediated upregulation of miR-18b was dependent on the increased binding of transcription factors Jun proto-oncogene (C-Jun) and v-Myc myelocytomatosis viral oncogene homolog (C-Myc) to miR-18b promoter region via phosphoinositide 3-kinase (PI3K)/AKT pathway. Finally, we further found that miR-18b directly suppressed the expression of CTGF in NPC. In clinical fresh specimens, miR-18b was widely overexpressed and inversely correlated with CTGF expression in NPC. Our studies are the first to demonstrate that reduced CTGF as an unfavorable prognosis factor mediates the activation of miR-18b, an oncomir directly suppresses CTGF expression, by PI3K/AKT/C-Jun and C-Myc and promotes cell growth of NPC.
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影响因子：
9
作者：
通讯作者：
--
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：
Ernst, A.;Campos, B.;Radlwimmer, B.
通讯作者：
Radlwimmer, B.
DOI：
10.1158/1078-0432.ccr-09-1736
发表时间：
2010-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Landi MT;Zhao Y;Rotunno M;Koshiol J;Liu H;Bergen AW;Rubagotti M;Goldstein AM;Linnoila I;Marincola FM;Tucker MA;Bertazzi PA;Pesatori AC;Caporaso NE;McShane LM;Wang E
通讯作者：
Wang E
影响因子：
64.8
作者：
O'Donnell, KA;Wentzel, EA;Mendell, JT
通讯作者：
Mendell, JT