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

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 G0/G1. 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.

• Authors: Lu-Lu Wang, Hui-Hui Guo, Yun Zhan, Chen-Lin Feng, Shuai Huang, Yan-Xing Han, Wen-Sheng Zheng, Jian-Dong Jiang
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 15 Pg. 25055-25065 (Apr 11 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28445988 (Publication Type: Journal Article)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p21
• RNA, Double-Stranded
• RNA, Small Untranslated

Topics

• Animals
• Apoptosis (genetics)
• Cell Cycle (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Cellular Senescence (genetics)
• Colorectal Neoplasms (genetics, pathology)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Disease Models, Animal
• Gene Expression Regulation, Neoplastic
• Gene Knockdown Techniques
• Heterografts
• Humans
• Male
• Mice
• RNA, Double-Stranded (genetics)
• RNA, Small Untranslated (genetics)
• Tumor Burden