LINC01140通过miR-452-5p/Wnt/β-catenin轴调控食管鳞状细胞癌Eca109细胞的增殖与侵袭  

LINC01140 regulates the proliferation and invasion of esophageal squamous cell carcinoma Eca109 cells via miR-452-5p/Wnt/β-catenin axis

作　　者：郭艳丽[1] 尹情 韩俊淑 郭炜[1] 沈素朋[1] 梁佳[1] 董稚明[1] GUO Yanli;YIN Qing;HAN Junshu;GUO Wei;SHEN Supeng;LIANG Jia;DONG Zhiming(Hebei Provincial Cancer Institute,the Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,Hebei,China)

机构地区：[1]河北医科大学第四医院河北省肿瘤研究所,河北石家庄050011

出　　处：《中国肿瘤生物治疗杂志》2021年第9期900-907,共8页Chinese Journal of Cancer Biotherapy

基　　金：河北省自然科学基金资助项目(No.H2020206368);河北省医学科学研究重点课题计划项目(No.20210399);河北省人才工程培养资助项目(No.201901035)。

摘　　要：目的:探讨长链非编码RNA(lncRNA)LINC01140在食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织及细胞中的表达及其对Eca109细胞增殖与侵袭的影响及其分子机制。方法:选取2012年3月至2015年5月河北医科大学第四医院收治的133例ESCC患者的临床资料和GEPIA数据库中收集的182例ESCC组织及286例食管正常黏膜组织的LINC01140表达数据,以及ESCC细胞系Kyse150、Eca109和TE13。用qPCR法检测癌组织和细胞中LINC01140的表达水平,分析其表达水平与患者临床病理特征及预后的关系。分别将pcDNA3.1-LINC01140、阴性对照(pcDNA3.1-NC)或miR-452-5p mimic及阴性对照(miR-NC)转染到Eca109细胞,MTS、Transwell实验分别检测细胞的增殖与侵袭能力。用双荧光报告基因实验及TOP/FOP报告基因系统检测LINC01140与miR-452-5p的靶向结合作用及LINC01140对Wnt/β-catenin通路活化水平的影响。结果:LINC01140在ESCC组织和细胞中表达均显著下调(均P<0.01),LINC01140低表达与ESCC患者年龄、淋巴结转移、TNM分期及OS密切相关(均P<0.05)。LINC01140过表达明显抑制Eca109细胞的增殖及侵袭能力(均P<0.01)。机制研究表明,LINC01140可能通过竞争结合miR-452-5p影响Wnt/β-catenin信号通路的活化水平继而调控Eca109细胞的恶性生物学行为。结论:LINC01140通过靶向miR-452-5p/Wnt/β-catenin轴促进ESCC细胞的增殖与侵袭能力,其有望成为ESCC患者靶向治疗的潜在靶点及预后评估的标志物。Objective:To investigate the expression of lncRNA LINC01140 in esophageal squamous cell carcinoma(ESCC)tissues and cell lines,and to explore its effect on the proliferation and invasion of Eca109 cells as well as the possible molecular mechanism.Methods:The clinical data of 133 ESCC patients who were treated in the Fourth Hospital of Hebei Medical University from March 2012 to May 2015 and the data of 182 ESCC tissues and 286 normal esophageal mucosa tissues included in GEPIA database,as well as ESCC cell lines(Kyse150,Eca109,TE13)were collected for this study.The expression level of LINC01140 in ESCC tissues and cell lines was detected by qPCR method,and the relationship between its expression level and clinicopathological features as well as the prognosis of ESCC patients was further analyzed.pcDNA3.1-LINC01140,negative control(pcDNA3.1-NC)or miR-452-5p mimics and negative control(miR-NC)were respectively transfected into Eca109 cells.Then,MTS and Transwell assay were performed to assess the effect of LINC01140 on proliferation and invasion of transfected cells.The interaction between LINC01140 and miR-452-5p,as well as the effect of LINC01140 on the activation of Wnt/β-catenin pathway was detected by Dual-luciferase reporter gene assay and TOP/FOP reporter gene system.Results:The expression of LINC01140 was downregulated in ESCC tissues and cell lines(all P<0.01).Low expression of LINC01140 was closely correlated with the age,lymph node metastasis,TNM stage and the OS of ESCC patients(all P<0.01).Overexpression of LINC01140 significantly reduced the proliferation and invasion ability of Eca109 cells(all P<0.01).Mechanistic analysis indicated that LINC01140 affected the activation of Wnt/β-catenin signaling pathway possibly via competitively sponging miR-452-5p to further regulate the malignant biological behaviors of Eca109 cells.Conclusion:LINC01140 affects proliferation and invasion of ESCC cells via regulating miR-452-5p/Wnt/β-catenin axis.LINC01140 is expected to be a potential target for the targeted t

关 键 词：食管鳞状细胞癌 ECA109细胞 LINC01140 miR-452-5p WNT/Β-CATENIN信号通路 增殖 侵袭 

分 类 号：R735.1[医药卫生—肿瘤] R730.2[医药卫生—临床医学]