MiR-663, a microRNA targeting p21waf1/CIP1, promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma
MiR-663, a microRNA targeting p21waf1/CIP1, promotes the proliferation and tumorigenesis of nasopharyngeal carcinoma
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DOI：
10.1038/onc.2011.629
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发表时间：
2012-10-01
期刊：
影响因子：
8
通讯作者：
Yun, J-P
中科院分区：
文献类型：
--
作者：
Yi, C.;Wang, Q.;Yun, J-P
MicroRNA (miRNA) 在不同肿瘤类型的恶性进展中可能充当癌基因或抑癌基因。最近有报道称 MiR-663 减少并被确定为胃癌中的肿瘤抑制因子。我们还验证了它在抑制胃癌细胞系细胞增殖中的作用。然而，在这项研究中，使用 miRNA 微阵列发现，与人永生化鼻咽上皮细胞相比，miR-663 在鼻咽癌 (NPC) 细胞中表达上调，并且这种较高的表达在 NPC 组织样本中得到证实。事实上，抑制 miR-663 会损害体外 NPC 细胞的增殖以及裸鼠异种移植物的 NPC 肿瘤生长。从机制上讲，miR-663直接靶向p21（WAF1/CIP1）来促进细胞G1/S转变，因为miR-663对G1/S转变的抑制作用可以通过p21（WAF1/CIP1）沉默来挽救。我们的结果表明 miR-663 可能作为鼻咽癌的癌基因。新发现的miR-663/p21(WAF1/CIP1)轴阐明了鼻咽癌细胞增殖的分子机制，为鼻咽癌患者的诊断和治疗提供了新的策略。癌基因 (2012) 31, 4421-4433; doi：10.1038/onc.2011.629； 2012 年 1 月 16 日在线发布
MicroRNAs (miRNAs) may function as either oncogenes or tumor suppressors in the malignant progression of different tumor types. MiR-663 was recently reported to be decreased and identified as a tumor suppressor in gastric cancer. We also verified its role in repressing cell proliferation of a gastric cancer cell line. In this study, however, miR-663 was found to be upregulated in nasopharyngeal carcinoma (NPC) cells compared with human immortalized nasopharyngeal epithelium cells, using a miRNA microarray, and this higher expression was confirmed in NPC tissue samples. Indeed, inhibition of miR-663 impaired the proliferation of NPC cells in vitro and the NPC tumor growth of xenografts in nude mice. Mechanistically, miR-663 directly targeted p21(WAF1/CIP1) to promote the cellular G1/S transition, as the inhibitory effects of miR-663 on the G1/S transition could be rescued by p21(WAF1/CIP1) silencing. Our results imply that miR-663 may act as an oncogene in NPC. The newly identified miR-663/p21(WAF1/CIP1) axis clarifies the molecular mechanism of NPC cell proliferation and represents a novel strategy for the diagnosis and treatment of patients with NPC. Oncogene (2012) 31, 4421-4433; doi: 10.1038/onc.2011.629; published online 16 January 2012