State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Oncogene. 2012 Oct 11;31(41):4421-33. doi: 10.1038/onc.2011.629. Epub 2012 Jan 16.
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.
微小 RNA（miRNAs）在不同肿瘤类型的恶性进展中可能作为癌基因或肿瘤抑制因子发挥作用。最近有研究报道 miR-663 在胃癌中下调，并被鉴定为肿瘤抑制因子。我们还验证了其在抑制胃癌细胞系增殖中的作用。然而，在本研究中，与永生化鼻咽上皮细胞相比，miRNA 微阵列显示 miR-663 在鼻咽癌（NPC）细胞中上调，并且在 NPC 组织样本中得到了进一步证实。事实上，抑制 miR-663 可损害 NPC 细胞在体外的增殖和裸鼠异种移植 NPC 肿瘤的生长。在机制上，miR-663 可直接靶向 p21(WAF1/CIP1) 以促进细胞 G1/S 期转换，因为 miR-663 对 G1/S 期转换的抑制作用可被 p21(WAF1/CIP1) 沉默所挽救。我们的研究结果表明，miR-663 可能在 NPC 中作为癌基因发挥作用。新鉴定的 miR-663/p21(WAF1/CIP1) 轴阐明了 NPC 细胞增殖的分子机制，代表了 NPC 患者诊断和治疗的新策略。
