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2017 ; 8
(15
): 25055-25065
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Specific up-regulation of p21 by a small active RNA sequence suppresses human
colorectal cancer growth
#MMPMID28445988
Wang LL
; Guo HH
; Zhan Y
; Feng CL
; Huang S
; Han YX
; Zheng WS
; Jiang JD
Oncotarget
2017[Apr]; 8
(15
): 25055-25065
PMID28445988
show ga
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.
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