Screening of potential molecular targets for colorectal cancer therapy

Kimi Honma¹, Ichiro Takemasa², Ryo Matoba³, Yusuke Yamamoto¹, Fumitaka Takeshita¹, Masaki Mori², Morito Monden², Kenichi Matsubara³, Takahiro Ochiya¹

¹Section for Studies on Metastasis, National Cancer Center Research Institute, Tokyo, Japan; ²Graduate School of Medicine, Osaka University, Osaka, Japan; ³DNA Chip Research Inc., Yokohama, Japan

Abstract: Colorectal cancer is a leading cause of cancer death worldwide. To identify molecular targets for colorectal cancer therapy, we tested small interfering RNAs (siRNAs) against 97 genes whose expression was elevated in human colorectal cancer tissues for the ability to promote apoptosis of human colorectal cancer cells (HT-29 cells). The results indicate that the downregulation of PSMA7 (proteasome subunit, α-type, 7) and RAN (ras-related nuclear protein) most efficiently induced apoptosis of HT-29 cells. PSMA7 and RAN were highly expressed in colorectal cancer cell lines compared with normal colon tissues. Furthermore, PSMA7 and RAN were overexpressed in not only colon tumor tissues but also the other tumor tissues. Moreover, in vivo delivery of PSMA7 siRNA and RAN siRNA markedly induced apoptosis in HT-29 xenograft tumors in mice. Thus, silencing of PSMA7 and RAN induces cancer cells to undergo apoptosis, and PSMA7 and RAN might be promising new molecular targets for drug and RNA interference-based therapeutics against colorectal cancer.

Keywords: colorectal cancer, molecular target, RNAi, PSMA7, RAN