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赖氨酸特异性去甲基化酶1(LSD1)对结肠癌细胞侵袭和转移的影响及机制

[The influence and mechanisms of lysine-specific demethylase 1 (LSD1) on invasion and metastasis of colon cancer cells].

作者信息

Ding J, Zhang Z M, Dong Q, Mi R, Xu K S, Yang X F, Liao G Q

机构信息

Department of Gastrointestinal Surgery, Gui Zhou Provincial People's Hospital, Guiyang 550002, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2017 Mar 14;97(10):743-748. doi: 10.3760/cma.j.issn.0376-2491.2017.10.006.

DOI:10.3760/cma.j.issn.0376-2491.2017.10.006
PMID:28316154
Abstract

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.

摘要

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。

相似文献

1
[The influence and mechanisms of lysine-specific demethylase 1 (LSD1) on invasion and metastasis of colon cancer cells].赖氨酸特异性去甲基化酶1(LSD1)对结肠癌细胞侵袭和转移的影响及机制
Zhonghua Yi Xue Za Zhi. 2017 Mar 14;97(10):743-748. doi: 10.3760/cma.j.issn.0376-2491.2017.10.006.
2
Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells.在结肠癌细胞中鉴定受LSD1调控的下游转移相关靶基因。
Oncotarget. 2017 Mar 21;8(12):19609-19630. doi: 10.18632/oncotarget.14778.
3
Interference of lysine-specific demethylase 1 inhibits cellular invasion and proliferation in vivo in gastric cancer MKN-28 cells.赖氨酸特异性去甲基化酶 1 的干扰抑制胃癌 MKN-28 细胞体内的细胞侵袭和增殖。
Biomed Pharmacother. 2016 Aug;82:498-508. doi: 10.1016/j.biopha.2016.04.070. Epub 2016 Jun 2.
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LSD1-mediated epigenetic modification contributes to proliferation and metastasis of colon cancer.LSD1 介导的表观遗传修饰促进结肠癌的增殖和转移。
Br J Cancer. 2013 Aug 20;109(4):994-1003. doi: 10.1038/bjc.2013.364. Epub 2013 Jul 30.
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Positive expression of LSD1 and negative expression of E-cadherin correlate with metastasis and poor prognosis of colon cancer.LSD1 阳性表达和 E-钙黏蛋白阴性表达与结肠癌的转移和预后不良相关。
Dig Dis Sci. 2013 Jun;58(6):1581-9. doi: 10.1007/s10620-012-2552-2. Epub 2013 Jan 12.
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Inhibition of LSD1 by Pargyline inhibited process of EMT and delayed progression of prostate cancer in vivo.帕吉林对赖氨酸特异性去甲基化酶1(LSD1)的抑制作用可抑制上皮-间质转化(EMT)过程,并延缓体内前列腺癌的进展。
Biochem Biophys Res Commun. 2015 Nov 13;467(2):310-5. doi: 10.1016/j.bbrc.2015.09.164. Epub 2015 Oct 3.
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[Effects of N-cadherin expression on cell cycle, cell apoptosis and invasiveness and metastasis of tongue squamous cell carcinoma cell line Tca8113 cells].N-钙黏蛋白表达对舌鳞状细胞癌细胞系Tca8113细胞周期、细胞凋亡及侵袭转移的影响
Zhonghua Kou Qiang Yi Xue Za Zhi. 2011 Jun;46(6):365-9. doi: 10.3760/cma.j.issn.1002-0098.2011.06.012.
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LSD1-mediated epigenetic modification contributes to ovarian cancer cell migration and invasion.赖氨酸特异性去甲基化酶1(LSD1)介导的表观遗传修饰促进卵巢癌细胞的迁移和侵袭。
Oncol Rep. 2016 Jun;35(6):3586-92. doi: 10.3892/or.2016.4729. Epub 2016 Apr 4.
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Silencing of LSD1 gene modulates histone methylation and acetylation and induces the apoptosis of JeKo-1 and MOLT-4 cells.沉默 LSD1 基因可调节组蛋白甲基化和乙酰化,并诱导 JeKo-1 和 MOLT-4 细胞凋亡。
Int J Mol Med. 2017 Aug;40(2):319-328. doi: 10.3892/ijmm.2017.3032. Epub 2017 Jun 19.
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CXCL12 gene silencing down-regulates metastatic potential via blockage of MAPK/PI3K/AP-1 signaling pathway in colon cancer.CXCL12 基因沉默通过阻断 MAPK/PI3K/AP-1 信号通路降低结肠癌的转移潜能。
Clin Transl Oncol. 2018 Aug;20(8):1035-1045. doi: 10.1007/s12094-017-1821-0. Epub 2018 Jan 5.

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