lncRNA GAS5 enhances the radiosensitivity of colon cancer cells by down-regulating miR-223 expression / 中华放射医学与防护杂志

ABSTRACT

Objective To explore the effect of lncRNA of growth arrest-specific 5 (lncRNA GAS5) on the radiosensitivity of colon cancer cells by targeting miR-223.Methods The expressions of lncRNA GAS5 in a few of colon cancer cell lines were detected by real-time quantitative PCR (qPCR).The cell lines with low expression level of lncRNA GAS5 were selected for subsequent study.The effect of overexpression of lncRNA GAS5 on the radiosensitivity of colon cancer SW480 cells was detected by cell cloning experiments.The target gene miR-223 of lncRNA GAS5 was predicted and validated by the bioinformatics database starBase and dual luciferase reporter assays.qPCR was used to detect the expression of miR-223 in various colon cancer cell lines and the influence of lncRNA GAS5 overexpression on the expression of miR-223 in SW480 cells.Results Compared with normal human colonic epithelial cells (NCM460),the expressions of lncRNA GAS5 in the colon cancer SW480,LOVO,HT-29 and SW620 cell lines were significantly lower(t =15.25,8.69,14.42,11.62,P ＜ 0.05),with the lowest level in SW480 cells.Both overexpression of lncRNA GAS5 and down-regulation of miR-223 significantly increased the radiosensitivity of colon cancer cells by decreasing cell survival fraction (at 8 Gy,lncRNA GAS5,t =13.51,P ＜ 0.05;anti-miR-223,t =14.93,P ＜ 0.05)and promoting apoptosis (lncRNA GAS5,t =8.30,P ＜ 0.05;anti-miR-223,t =7.32,P ＜ 0.05).Bioinformatics analysis showed that the 3'sequence of lncRNA GAS5 contained the binding sites with miR-223.After overexpression or downregulation of lncRNA GAS5,the expression of miR-223 was enhanced or reduced.Conclusions The lncRNA GAS5 promotes the apoptosis of colon cancer cells and inhibits its survival by targeting miR-223 expression,thereby increases the radiosensitivity of colon cancer cells.