lncRNA SNHG20抑制结肠癌细胞化疗敏感性的机制  

lncRNA SNHG20 promotes chemoresistance in colorectal cancer

作　　者：何樱[1] 黄维甄[1] 欧阳考滨[1] 袁霞[1] 

机构地区：[1]惠州市中心人民医院肿瘤内科,广东惠州516000

出　　处：《现代肿瘤医学》2017年第15期2361-2365,共5页Journal of Modern Oncology

基　　金：惠州市民政局资助项目(编号:20151116344);惠州市科技计划项目(编号:20150801)

摘　　要：目的:探讨长链非编码RNA(long non-coding RNA,lncRNA)SNHG20抑制结肠癌细胞对5-FU化疗敏感性的调控机制。方法:利用结肠癌细胞株Lo Vo构建对5-FU抵抗的细胞株Lo Vo/5-FU,通过qRTPCR的方法检测Lo Vo/5-FU中lncRNA SNHG20的表达情况。进一步分别构建lncRNA SNHG20稳定过表达及表达沉默的结肠癌细胞株,利用CCK-8的方法检测lncRNA SNHG20对5-FU IC50的影响,通过平板克隆形成实验检测lncRNA SNHG20对克隆形成能力的影响。最后运用Western blot方法探讨lncRNA SNHG20抑制结肠癌对5-FU化疗敏感性的调控机制。结果:在对5-FU耐药的结肠癌细胞株Lo Vo/5-FU中,lncRNA SNHG20显著高表达(P<0.001)。lncRNA SNHG20高表达能明显提高5-FU的IC50,而沉默lncRNA SNHG20则显著提高Lo Vo/5-FU对5-FU的敏感性(P<0.001)。平板克隆形成实验结果显示lncRNA SNHG20显著提高细胞的克隆形成能力(P<0.001)。Western blot结果表明,lncRNA SNHG20能显著抑制结肠癌细胞株PTEN蛋白的表达,而p-AKT及p-PI3K表达水平明显上调。结论:lncRNA SNHG20通过调控PTEN/PI3K/AKT信号通路抑制结肠癌细胞对5-FU的化疗敏感性。Objective： To explore the effect of lncRNA SNHG20 on the chemoresistance of colorectal cancer and its underlying mechanism. Methods： 5-fluorouracil resistance colorectal cell line Lo Vo/5-FU was constructed to evaluate the expression of lncRNA SNHG20 in parental Lo Vo and Lo Vo/5-FU cells. Gain of function and loss of function assays were further used to investigate the effect of lncRNA SNHG20 on the 5-fluorouracil resistance of Lo Vo cells. Results： lncRNA SNHG20 was highly up-regulated in Lo Vo/5-FU cells in comparison with parental Lo Vo cells（ P 0. 001）. Furthermore,overexpression of lncRNA SNHG20 significantly reduced the sensitivity to 5-FU in Lo Vo cells,whereas silencing lncRNA SNHG2 0 increased the sensitivity to 5-FU in Lo Vo/5-FU cells（ P 0. 001）. Clone formation assay revealed that up-regulation of lncRNA SNHG20 obviously promotes cellular clonality in Lo Vo cells. On the contrary,knocked down of lncRNA SNHG20 visibly reduced colony forming ability in Lo Vo/5-FU cells（ P 0. 001）. In addition,Western blot indicated that lncRNA SNHG20 reduced the expression of PTEN,whereas up-regulated the expression of p-AKT and p-PI3 K in Lo Vo cells. Consistently,knocked down of lncRNA SNHG20 in Lo Vo/5-FU cells had the opposite effects on the expression of PTEN,p-AKT and p-PI3 K. Conclusion： lncRNA SNHG20 promotes resistance to 5-FU in colorectal cancer via PTEN/PI3K/AKT signal pathway.

关 键 词：结肠癌 5-FU 化疗 lncRNA SNHG20 

分 类 号：R735.35[医药卫生—肿瘤]