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下调LncRNA DLX6-AS1通过miR-144调控 FBXW7表达影响食管癌Eca-109细胞的增殖、侵袭和EMT进程
作者:张鹤1  胡琰琰2  陈平3  李秋文2  肖文华2 
单位:1. 中国人民解放军总医院第四医学中心 肿瘤内科, 北京 100142;
2. 中国人民解放军第五医学中心 肿瘤内科, 北京 100071;
3. 中国人民解放军总医院第四医学中心 胸外科, 北京 100142
关键词:长非编码RNA远端少同源盒6反义1 miR-144 FBXW7 Eca-109细胞 增殖 侵袭 
分类号:R735.1
出版年·卷·期(页码):2022·50·第八期(959-967)
摘要:

目的:评估长非编码RNA远端少同源盒6反义1(lncRNA DLX6-AS1)在食管癌发生发展中的作用及其潜在的机制。方法:采用qRT-PCR检测lncRNA DLX6-AS1和miR-144、FBXW7在食管癌组织及癌旁正常组织中的mRNA表达。分别敲低lncRNA DLX6-AS1和miR-144、FBXW7在Eca-109细胞中的表达后,采用CCK-8法检测细胞生长活性,细胞克隆形成实验检测细胞增殖,Transwell法检测细胞侵袭,Western blot检测E-cadherin、Vimentin和GAPDH的表达。采用miRanda、TargetScan和双荧光素酶报告基因检测验证lncRNA DLX6-AS1和miR-144、miR-144和FBXW7之间的靶向关系。结果:食管癌组织中lncRNA DLX6-AS1和FBXW7表达显著高于癌旁正常组织,miR-144表达与癌旁组织对比明显下调。lncRNA DLX6-AS1、FBXW7表达下降后,Eca-109细胞增殖、侵袭与EMT能力也明显下调;LncRNA DLX6-AS1与miR-144、miR-144与FBXW7呈靶向负调控关系;miR-144表达下降后,Eca-109细胞增殖、侵袭与EMT能力显著上调;上调LncRNA DLX6-AS1靶向miR-144促进Eca-109细胞增殖、侵袭与EMT。结论:Lnc RNA DLX6-AS1在食管癌中表达上调且通过miR-144/FBXW7轴促进Eca-109细胞增殖、侵袭和EMT。

Objective: To evaluate the role of lncRNA DLX6-AS1 in the development and progression of esophageal cancer and its potential mechanism.Methods: qRT-PCRwas used to detect the mRNA expressions of lncRNA DLX6-AS1,miR-144 and FBXW7 in esophageal cancer tissues and adjacent normal tissues.After knockdown of lncRNA DLX6-AS1,miR-144 and FBXW7 in Eca-109 cells,cell growth activity was detected by CCK-8 assay,cell proliferation was detected by cell clonogenesis assay.And cell invasion was detected by Transwell assay.Western blot was used to detect the expression of E-cadherin,Vimentin and GAPDH.miRanda,TargetScan and dual luciferase reporter gene assays were used to verify the targeting relationship between lncRNA DLX6-AS1 and miR-144 and between miR-144 and FBXW7.Results: The expression of lncRNA DLX6-AS1 and FBXW7 in esophageal cancer tissues was significantly higher than that in normal adjacent tissues,and the expression of miR-144 was significantly down-regulated compared with that in adjacent tissues.After the expression of lncRNA DLX6-AS1 and FBXW7 decreased,the proliferation,invasion and EMT ability of Eca-109 cells were also significantly down-regulated.LncRNA DLX6-AS1 was negatively regulated by mR-144,and mR-144 was negatively regulated by FBXW7.The proliferation,invasion and EMT ability of Eca-109 cells were significantly up-regulated after the down-regulation of miR-144 expression.Upregulation of LncRNA DLX6-AS1 targeting miR-144 promotes Eca-109 cell proliferation,invasion and EMT.Conclusion: LncRNA DLX6-AS1 is up-regulated in esophageal carcinoma and promotes Eca-109 cell proliferation,invasion and EMT through miR-144/FBXW7 axis.

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