Wang Qingfei, Li Meixing, Wang Ying, Zhang Yong, Jin Shu, Xie Guohua, Liu Zhengchun, Wang Shujun, Zhang Huizhen, Shen Lisong, Ge Hailiang
Shanghai Institute of Immunology, School of Medicine, Shanghai Jiaotong University, 280 South Chongqing Road, Shanghai 200025, PR China.
Cancer Lett. 2008 Sep 28;269(1):127-38. doi: 10.1016/j.canlet.2008.04.035. Epub 2008 Jun 4.
CML66 is a novel, promising tumor antigen; however, its biological roles remain unclear. In present study, we applied a short hairpin RNA triggered RNA interfering to suppress CML66 expression in HeLa cervical carcinoma cells. Knockdown of CML66 inhibited proliferation, migration and invasion activities of HeLa cells in vitro. Meanwhile, in nude mice, CML66 silencing suppressed tumor growth and pulmonary metastasis with HeLa cells injected subcutaneously. Furthermore, using metastasis-related genes cDNA microarrays, we found 9 genes were significantly down-regulated after CML66 silencing, including cathepsin L, MMP15, uPAR, VEGF, COX-2, S100A4, MUC1, MDM2 and RAC1. These results imply that CML66 may play an oncogenic role in ways of favoring tumor cells proliferation, invasion and metastasis-associated with multiple pathways. Thus, CML66 might be a potential target for development of cancer therapy.
CML66是一种新型的、有前景的肿瘤抗原；然而，其生物学作用仍不清楚。在本研究中，我们应用短发夹RNA触发的RNA干扰来抑制人宫颈癌HeLa细胞中CML66的表达。敲低CML66可抑制HeLa细胞在体外的增殖、迁移和侵袭活性。同时，在裸鼠中，沉默CML66可抑制皮下注射HeLa细胞后的肿瘤生长和肺转移。此外，使用转移相关基因cDNA微阵列，我们发现CML66沉默后有9个基因显著下调，包括组织蛋白酶L、基质金属蛋白酶15、尿激酶型纤溶酶原激活物受体、血管内皮生长因子、环氧合酶-2、S100A4、粘蛋白1、小鼠双微体2和RAC1。这些结果表明，CML66可能通过促进肿瘤细胞增殖、侵袭和与多种途径相关的转移来发挥致癌作用。因此，CML66可能是癌症治疗开发的一个潜在靶点。
