RNA interference targeting CML66, a novel tumor antigen, inhibits proliferation, invasion and metastasis of HeLa cells.
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.
Wang
Qingfei
Q
Shanghai Institute of Immunology, School of Medicine, Shanghai Jiaotong University, 280 South Chongqing Road, Shanghai 200025, PR China.
Li
Meixing
M
Wang
Ying
Y
Zhang
Yong
Y
Jin
Shu
S
Xie
Guohua
G
Liu
Zhengchun
Z
Wang
Shujun
S
Zhang
Huizhen
H
Shen
Lisong
L
Ge
Hailiang
H
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000502:physiology*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D051546:Cyclooxygenase 2 / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D020782:Matrix Metalloproteinases / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018396:Mucin-1 / Q000502:physiology; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000209:etiology*; D034622:RNA Interference; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D000951:Antigens, Neoplasm; C060192:MUC1 protein, human; D018396:Mucin-1; C431278:NUDCD1 protein, human; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2; D020782:Matrix Metalloproteinases