上调LncRNA TUG1通过海绵miR-133a和激活Wnt/β-catenin信号通路对口腔鳞癌的影响  

Effect of Up-regulation of LncRNA TUG1 on Oral Squamous Cell Carcinoma through MiR-133a and Activation of Wnt/β-catenin Signaling Pathway

作　　者：朱磊 夏智敏 王尘帅 李锟[4] ZHU Lei;XIA Zhi-min;WANG Chen-shuai;LI Kun(Department of Stomatology,Jiangbei Hospital of Wuhan Union Medical College,Wuhan 430100,China;Department of Stomatology,School of Medical Vocational and Technology of Wuhan University,Wuhan 430060,China;Department of Maxillofacial Surgery,the First People's Hospital of Tianmen City,Tianmen,Hubei 431700,China;Department of General Surgery,Central South Hospital of Wuhan University,Wuhan 430000,China)

机构地区：[1]武汉市协和江北医院口腔科,武汉430100 [2]武汉大学医学职业技术学院口腔系,武汉430060 [3]天门市第一人民医院颌面外科,湖北天门431700 [4]武汉大学中南医院普外科,武汉430000

出　　处：《解放军医药杂志》2022年第2期16-23,共8页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

摘　　要：目的探讨LncRNA TUG1通过miR-133a对口腔鳞癌Cal27细胞的影响及其潜在的作用机制。方法选择2020年10月—2021年5月确诊的口腔鳞癌组织50例及癌旁正常组织40例。通过实时荧光定量PCR检测LncRNA TUG1和miR-133a在口腔鳞癌组织、癌旁正常组织、口腔鳞癌Cal27细胞和口腔上皮HIOEC细胞中的差异表达;检测下调TUG1对Cal27细胞活力、侵袭及上皮间质转化(EMT)的影响。生物信息学软件miRanda预测LncRNA TUG1和miR-133a间的靶向关系,双荧光素酶报告基因实验检测TUG1和miR-133a的相关性。下调miR-133a表达,检测Cal27细胞增殖、侵袭和EMT能力。pcDNA-TUG1和miR-133a mimics共转染Cal27细胞,检测LncRNA TUG1通过miR-133a对Cal27细胞增殖、侵袭和EMT的影响。过表达或下调TUG1表达后,蛋白免疫印迹试验检测β-catenin、Cyclin D1和c-myc蛋白表达量,XAV939作用Cal27细胞,检测过表达TUG1对Cal27细胞增殖、侵袭和EMT的影响。结果与癌旁正常组织比较,口腔鳞癌组织中LncRNA TUG1的表达上调,miR-133a表达下调(P<0.01)。与HIOEC细胞比较,Cal27细胞中LncRNA TUG1的表达上调,miR-133a表达下调(P<0.01)。下调LncRNA TUG1表达明显抑制了Cal27细胞增殖、侵袭与EMT;LncRNA TUG1靶向且负调控miR-133a;下调miR-133a促进Cal27细胞增殖、侵袭与EMT;上调LncRNA TUG1通过miR-133a促进Cal27细胞增殖、侵袭与EMT。上调LncRNA TUG1激活了Cal27细胞内Wnt/β-catenin信号通路,并通过此通路促进Cal27细胞增殖、侵袭与EMT。结论上调LncRNA TUG1通过miR-133a和激活Wnt/β-catenin信号通路促进口腔鳞癌的发展。Objective To investigate effect of LncRNA TUG1 on oral squamous cell carcinoma Cal27 cells through miR-133a and its potential mechanism.Methods A total of 50 cases of oral squamous cell carcinoma diagnosed between October 2020 and May 2021 and 40 cases of adjacent normal tissues were selected.The differential expressions of LncRNA TUG1 and miR-133a in oral squamous cell carcinoma tissues,adjacent normal tissues,oral squamous cell carcinoma Cal27 cells and oral epithelial HIOEC cells were detected by real-time fluorescent quantitative polymerase chain reaction.Effects of down-regulation of TUG1 on viability,invasion and epithelial-mesenchymal transition(EMT)of Cal27 cells were detected.The miRanda bioinformatics software predicted the targeting relationship between LncRNA TUG1 and miR-133a,and the correlation between TUG1 and miR-133a was detected by dual luciferase reporter gene assay.The miR-133a expression was down-regulated to detect proliferation,invasion and EMT ability of Cal27 cells.Cal27 cells were co-transfected with pcDNA-TUG1 and miR-133a mimics to detect effects of LncRNA TUG1 on proliferation,invasion and EMT of Cal27 cells via miR-133a.After overexpression or down-regulation of TUG1,protein expressions ofβ-catenin,Cyclin D1 and c-myc were detected by Western blot,and Cal27 cells were treated with XAV939 to detect effects of overexpression of TUG1 on proliferation,invasion and EMT of Cal27 cells.Results Compared with those in adjacent normal tissues,LncRNA TUG1 expression was up-regulated,while miR-133a expression was down-regulated in oral squamous cell carcinoma tissues(P<0.01)Compared with those in HIOEC cells,LncRNA TUG1 expression was up-regulated,while miR-133a expression was down-regulated in Cal27 cells(P<0.01).Down-regulation of LncRNA TUG1 significantly inhibited proliferation,invasion and EMT of Cal27 cells.LncRNA TUG1 targeted and negatively regulated miR-133a.Down-regulation of miR-133a promoted proliferation,invasion and EMT of Cal27 cells.Up-regulation of LncRNA TUG1 promoted prolifer

关 键 词：口腔肿瘤 癌 鳞状细胞 LncRNA TUG1 miR-133a WNT/Β-CATENIN Cal27细胞 细胞增殖 肿瘤侵润 

分 类 号：R739.8[医药卫生—肿瘤]