title: Knockdown of RCK/p54 expression by RNAi inhibits proliferation of human colorectal cancer cells in vitro and in vivo.
abstract: Colorectal cancer is the third most common cancer in both men and women around the world. Although much progress of the mechanism of colorectal carcinogenesis has been made, the studies centering on the mechanisms of tumorigenesis are much needed to be further exploited. The overexpression of RCK/p54 gene, a member of the DEAD box protein/RNA helicase family, has been found in this malignancy. Roles of RCK in the development of colon cancer, however, are unknown. In this report, we explored whether RCK/p54 plays a role in maintaining the malignant phenotype and functions in the canonical Wnt signaling pathway of colorectal cancer cells harboring an APC mutation. The ectopic overexpression of RCK/p54 gene in colorectal cancer cells by transfection with RCK/p54 cDNA could lead to a significant increase of Tcf transcriptional activity and expression levels of Wnt target genes. By RNAi assay, we also observed that the Tcf transcriptional activity in LoVo-shRNA cells was significantly decreased by approximately 61.3%, while the mRNA and protein expression levels of Wnt target genes were also obviously decreased. Furthermore, the anti-tumour effects and its possible mechanisms of actions in LoVo cells elicited by a decrease in the level of RCK/p54 by RNAi were examined. Results showed that RCK/p54 downregulation could significantly reduce the viability of LoVo cells, increased cell number of S phase, led to cell apoptosis induction, and inhibited tumor growth in nude mice. Taken together, RCK/ p54 might be a determinant of colorectal cancer proliferation by activating the canonical Wnt pathway and RCK/p54-shRNA might be a potential strategy for colorectal cancer gene therapy.
authors.affiliation: Department of Clinical Diagnosis, Tangdu Hospital, Fourth Military Medical University, Shaanxi Province, Xi'an, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Lin
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Shen
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.forename: Ping
authors.initials: P
authors.lastname: Gao
authors.forename: Ke
authors.initials: K
authors.lastname: Dong
authors.forename: Hui-Zhong
authors.initials: HZ
authors.lastname: Zhang