miR-203 Suppresses Tumor Growth and Angiogenesis by Targeting VEGFA in Cervical Cancer
miR-203 Suppresses Tumor Growth and Angiogenesis by Targeting VEGFA in Cervical Cancer
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DOI：
10.1159/000350125
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发表时间：
2013-01-01
影响因子：
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通讯作者：
Shi, Hong
中科院分区：
文献类型：
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作者：
Zhu, Xiangyu;Er, Kejun;Shi, Hong
背景/目的：MicroRNA（miRNA）在不同癌症的发生发展中起着重要作用。本研究旨在探讨miR-203在人宫颈癌中的作用及其机制。方法：采用qRT-PCR方法检测miR-203在宫颈癌组织及细胞株中的表达。通过甲基化特异性PCR检测miR-203启动子区域的甲基化状态。通过体外和体内测定确定miR-203的功能效应。结果：miR-203在宫颈癌肿瘤和细胞系中频繁下调。miR-203的这种下调与miR-203启动子的甲基化相关。此外，miR-203通过直接靶向其3 '非翻译区下调血管内皮生长因子α（VEGFA）表达。功能分析显示，miR-203抑制裸鼠宫颈癌细胞增殖、肿瘤生长和血管生成，而VEGFA的强制表达挽救了这种抑制作用。结论：我们的集体研究结果表明，miR-203通过靶向VEGFA发挥肿瘤抑制剂的作用，从而抑制肿瘤生长和血管生成。因此，miR-203可能是宫颈癌潜在的治疗靶点和预后标志物。版权所有（C）2013 S. Karger AG，巴塞尔
Background/Aims: MicroRNA (miRNA) plays important roles in the development of different cancers. In this study, we investigated the roles and mechanisms of miR-203 in human cervical cancer. Methods: miR-203 expression was detected in cervical cancer tumors and cell lines by qRT-PCR. The methylation status in the promoter region of miR-203 was examined by methylation-specific PCR. The functional effect of miR-203 was determined by both in vitro and in vivo assays. Results: miR-203 was frequently down-regulated in cervical cancer tumors and cell lines. This down-regulation of miR-203 was associated with methylation of the miR-203 promoter. Furthermore, miR-203 down-regulated vascular endothelial growth factor alpha (VEGFA) expression by directly targeting its 3'-untranslated region. Functional assays revealed that miR-203 suppressed cervical cancer cell proliferation, tumor growth, and angiogenesis in nude mice, whereas forced expression of VEGFA rescued this inhibitory effect. Conclusion: Our collective findings indicate that miR-203 functions as a tumor suppressor by targeting VEGFA, resulting in the inhibition of tumor growth and angiogenesis. Thus, miR-203 may be a potential therapeutic target and prognostic marker in cervical cancer. Copyright (C) 2013 S. Karger AG, Basel