Ding J, Zhang Z M, Dong Q, Mi R, Xu K S, Yang X F, Liao G Q
Department of Gastrointestinal Surgery, Gui Zhou Provincial People's Hospital, Guiyang 550002, China.
Zhonghua Yi Xue Za Zhi. 2017 Mar 14;97(10):743-748. doi: 10.3760/cma.j.issn.0376-2491.2017.10.006.
To investigate the effect and molecular mechanisms of LSD1 on proliferation and metastasis of colon cancer. The influence of down-regulated LSD1 expression on proliferation, invasion and apoptosis of colon cancer cells were detected by transwell invasion assay, cell proliferation assay and apoptosis assay, respectively. Three independent siRNAs targeting LSD1 (siRNA-1554, siRNA-705, and siRNA-1973) were transfected to SW620 cells to detect gene-silencing efficiency, and the result showed that the knockdown effect of siRNA-705 were better than the other two siRNAs at both mRNA and protein levels. Using siRNA-705 and pargyline (2.5 mmol/L), we performed transwell invasion assay, cell proliferation assay and apoptosis assay in SW620 cell lines, and found the significant suppression of invasion and growth. Cell apoptosis were induced by siRNA and pargyline (<0.05). Interestingly, up-regulation of E-cadherin and down-regulation of N-cadherin were observed after treated with siRNA-705 and pargyline for 72 hours. Inhibition of LSD1 could impair proliferation and invasiveness, and induce apoptosis of colon cancer cells . It leads to up-regulation of E-cadherin and down-regulation of N-cadherin. All of above may play important roles in invasion and metastasis of colon cancer.
探讨赖氨酸特异性去甲基化酶1(LSD1)对结肠癌增殖和转移的影响及其分子机制。分别通过Transwell侵袭实验、细胞增殖实验和凋亡实验检测下调LSD1表达对结肠癌细胞增殖、侵袭和凋亡的影响。将三种靶向LSD1的独立小干扰RNA(siRNA-1554、siRNA-705和siRNA-1973)转染至SW620细胞以检测基因沉默效率,结果显示siRNA-705在mRNA和蛋白质水平的敲低效果均优于其他两种siRNA。使用siRNA-705和反苯环丙胺(2.5 mmol/L),我们在SW620细胞系中进行了Transwell侵袭实验、细胞增殖实验和凋亡实验,发现侵袭和生长受到显著抑制。siRNA和反苯环丙胺诱导了细胞凋亡(<0.05)。有趣的是,用siRNA-705和反苯环丙胺处理72小时后,观察到E-钙黏蛋白上调和N-钙黏蛋白下调。抑制LSD1可损害结肠癌细胞的增殖和侵袭能力,并诱导其凋亡。它导致E-钙黏蛋白上调和N-钙黏蛋白下调。以上所有可能在结肠癌的侵袭和转移中发挥重要作用。