RNAi-mediated downregulation of urokinase plasminogen activator receptor inhibits proliferation, adhesion, migration and invasion in oral cancer cells.
RNA interference (RNAi) has emerged as an effective method to target specific genes for silencing. Overexpression of urokinase-type plasminogen activator receptor (uPAR) has been implicated in progression and metastasis of oral cancer. In our study, RNAi was introduced to downregulate the expression of uPAR in the highly malignant oral squamous cell carcinoma (OSCC) cells. Our data demonstrated that siRNA targeting of uPAR leads to the efficient and specific inhibition of endogenous uPAR mRNA and protein expression as determined by quantitative real-time RT-PCR and Western blotting. Furthermore, simultaneous silencing of uPAR resulted in a dramatic reduction of tumor cell proliferation activity, adhesion, migration and invasion in vitro compared to the controls. These findings provide further evidence for the involvement of uPAR in a variety of cancer key cellular events as a versatile signaling orchestrator, and suggest that RNAi-directed targeting of uPAR can be used as a potent and specific therapeutic tool for the treatment of oral cancer, especially in inhibiting and/or preventing cancer cell invasion and metastasis.
Liang
Xinhua
X
Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, No. 14, Sec. 3, Renminnan Road, Chengdu Sichuan 610041, People's Republic of China. liang.xinhua@mayo.edu
Yang
Xiaoqin
X
Tang
Yaling
Y
Zhou
Hao
H
Liu
Xian
X
Xiao
Lin
L
Gao
Jiarang
J
Mao
Zuyi
Z
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D034622:RNA Interference / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism*
D014568:Urokinase-Type Plasminogen Activator