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
复制标题
结缔组织生长因子的丧失作为不利的预后因素，通过 PI3K/AKT/C-Jun 和 C-Myc 激活 miR-18b，并促进鼻咽癌的细胞生长。
DOI：
10.1038/cddis.2013.216
复制
发表时间：
2013-06-13
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
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在鼻咽癌发生发展和预后中的作用及其分子基础几乎未见报道。在这项研究中，我们观察到CTGF表达下调与NPC进展和预后不良显著相关。CTGF基因的敲除可显著提高细胞在体内和体外的增殖能力。随后，我们发现CTGF的减少增加了miR-18 b的表达，这是一种促进细胞增殖的肿瘤抑制剂。此外，我们发现CTGF介导的miR-18 b上调的减弱依赖于转录因子Jun原癌基因（C-Jun）和v-Myc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-18 b启动子区域的结合增加。最后，我们进一步发现miR-18 b直接抑制了NPC中CTGF的表达。在临床新鲜标本中，miR-18b在鼻咽癌组织中普遍过表达，且与CTGF表达呈负相关。我们的研究首次证明CTGF作为一个不利的预后因子介导miR-18 b的活化，miR-18 b通过PI3K/AKT/C-Jun和C-Myc直接抑制CTGF的表达，并促进NPC细胞的生长。
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.
结缔组织生长因子的丧失作为不利的预后因素，通过 PI3K/AKT/C-Jun 和 C-Myc 激活 miR-18b，并促进鼻咽癌的细胞生长。
影响因子：
9
作者：
通讯作者：
--