LSD1体外促进子宫内膜癌细胞的增殖、迁移和侵袭  

LSD1 Promote the Proliferation and Migration of Endometrial Carcinoma

作　　者：陈柯冰 任琛琛[1] 杨立[1,2] 朱远航 赵昕玥[1] CHEN Kebing;REN Chenchen;YANG Li;ZHU Yuanhang;ZHAO Xinyue(Department of Gynecology,the Third Affiliated Hospital of Zhengzhou University,Zhengzhou 471000,China;Zhengzhou Key Laboratory of Endometrial Diseases,Zhengzhou 471000,China)

机构地区：[1]郑州大学第三附属医院妇科,河南郑州471000 [2]郑州市子宫内膜疾病防治重点实验室,河南郑州471000

出　　处：《河南医学研究》2022年第10期1750-1757,共8页Henan Medical Research

摘　　要：目的赖氨酸特异性去甲基化酶1(LSD1)已被报道在多种恶性肿瘤中发挥作用,但其在子宫内膜癌中的作用少有报道。本研究旨在探讨LSD1在子宫内膜癌中的作用及其可能的机制。方法在子宫内膜癌细胞系Ishikawa和HEC1A中分别使用慢病毒和质粒对LSD1进行敲除和过表达。通过定量逆转录聚合酶链反应(RT-qPCR)和蛋白质印迹法(WB)验证转染结果。采用CCK-8实验、集落形成实验、伤口愈合实验和transwell侵袭实验分别检测LSD1对子宫内膜癌细胞体外增殖、克隆、迁移和侵袭的影响。通过肿瘤异种移植实验验证LSD1对子宫内膜癌细胞增殖的影响。结果与正常子宫内膜组织相比,LSD1在子宫内膜癌中表达水平升高,与肿瘤的分期及分级有关,并影响患者的预后。下调LSD1后,CCK-8实验和集落形成实验显示子宫内膜癌细胞的增殖能力明显下降,伤口愈合实验显示细胞的迁移能力减弱,transwell侵袭实验则证实了细胞的侵袭能力随之降低,而上调LSD1后结果则相反。通过WB和免疫组化法发现CD9的表达水平随着LSD1的降低而升高。此外,下调LSD1可抑制Ishikawa和HEC1A细胞在体内的肿瘤发生。结论LSD1是一种致癌因子,能显著促进子宫内膜癌细胞的增殖、迁移和侵袭,并反向调控下游因子CD9,为其作为子宫内膜癌的治疗靶点提供了更多依据。Objective Lysine specific demethylase 1(LSD1)had been reported to play a role in a variety of malignancies,but its role in endometrial carcinoma had rarely been reported.The purpose of this study is to investigate the role of LSD1 in endometrial cancer and its possible mechanisms.Methods LSD1 was knocked down or overexpressed in endometrial carcinoma cell lines(Ishikawa and HEC1A)by lentivims or plasmid,respectively.The transfection results were verified by quantitative reverse transcriptase polymerase chain reaction(RT-qPCR)and western blot(WB).The effects of LSD1 on the proliferation,cloning,migration,and invasion of endometrial carcinoma cells in vitro were detected by CCK-8 assay,colony formation assay,wound healing assay and transwell invasion assay,respectively.The effect of LSD1 on proliferation of endometrial carcinoma in vivo was validated by tumor xenograft transplantation assay.Results LSD1 expression was elevated in endometrial carcinoma compared with normal endometrial tissue,which is related to tumor stage and grade,and it affected patient outcomes.After LSD1 was down-regulated,CCK-8 and colony formation assay showed a significant decrease in the proliferation ability of endometrial carcinoma cells,and wound healing assay showed a decrease in the migration ability of cells,and transwell invasion assay confirmed a decrease in the invasion ability of cells,while upregulation of LSD1 had the opposite result.It was found that the expression level of CD9 increased with the decrease of LSD1 by WB and immunohistochemistry.In addition,down regulation of LSD1 reduced the tumorigenesis of Ishikawa and HEC1A cells in vivo.Conclusion LSD1 was an oncogenic factor,and it can significantly promote cell proliferation,migration and invasion,and reverse regulate the downstream factor CD9,provide more evidence for LSD1 as a therapeutic target of endometrial carcinoma.

关 键 词：赖氨酸特异性去甲基化酶1 子宫内膜癌 CD9 增殖 

分 类 号：R737.3[医药卫生—肿瘤]