Specific up-regulation of p21 by a small active RNA sequence suppresses human colorectal cancer growth

// Lu-Lu Wang 1 , Hui-Hui Guo 1 , Yun Zhan 1 , Chen-Lin Feng 1 , Shuai Huang 1 , Yan-Xing Han 1 , Wen-Sheng Zheng 1 , Jian-Dong Jiang 1 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, People’s Republic of China Correspondence to: Yan-Xing Han, email: hanyanxing@imm.ac.cn Wen-Sheng Zheng, email: zhengwensheng@imm.ac.cn Jian-Dong Jiang, email: jiang.jdong@163.com Keywords: p21-saRNA-322, small active RNA (saRNA), colorectal cancer, tumor growth suppression, xenograft tumor mode Received: July 28, 2016      Accepted: November 22, 2016      Published: March 06, 2017 ABSTRACT The double stranded small active RNA (saRNA)- p21-saRNA-322 inhibits tumor growth by stimulating the p21 gene expression. We focused our research of p21-saRNA-322 on colorectal cancer because 1) p21 down-regulation is a signature abnormality of the cancer, and 2) colorectal cancer might be a suitable target for in situ p21-saRNA-322 delivery. The goal of the present study is to learn the activity of p21-saRNA-322 in colorectal cancer. Three human colorectal cancer cell lines, HCT-116, HCT-116 (p53–/–) and HT-29 were transfected with the p21-saRNA-322. The expression of P21 protein and p21 mRNA were measured using the Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). The effect of p21-saRNA-322 on cancer cells was evaluated in vitro ; and furthermore, a xenograft colorectal tumor mode in mice was established to estimate the tumor suppressing ability of p21-saRNA-322 in vivo . The results showed that in all three colorectal cancer cell lines, the expression of p21 mRNA and P21 protein were dramatically elevated after p21-saRNA-322 transfection. Transfection of p21-saRNA-322 caused apoptosis and cell cycle arrest at the G 0 /G 1 . Furthermore, anti-proliferation effect, reduction of colonies formation and cell senescence were observed in p21-saRNA-322 treated cells. Animal studies showed that p21-saRNA-322 treatment significantly inhibited the HT-29 tumor growth and facilitated p21 activation in vivo . These results indicated that, p21-saRNA-322-induceded up-regulation of p21 might be a promising therapeutic option for the treatment of colorectal cancer.