lncRNA MALAT1通过调控miR-200a-3p/PD-L1轴促进结肠癌发展  

LncRNA MALAT1 contributes to colon cancer progression via modulating miR-200a-3p/PD-L1 axis

作　　者：周海燕 孙书林 金锦莲[1,2] 彭玲 徐明明 ZHOU Hai-yan;SUN Shu-lin;JIN Jin-lian;PENG Ling;XU Ming-ming(Department of Gastroenterology,Third Clinical Hospital,Three Gorges University,Yichang 443002,China;Department of Gastroenterology,Gezhouba Central Hospital of Sinopharm,Yichang443002,China)

机构地区：[1]三峡大学第三临床医学院消化内科,宜昌443002 [2]国药葛洲坝集团中心医院消化内科,宜昌443002

出　　处：《现代免疫学》2020年第6期488-496,共9页Current Immunology

摘　　要：为探究结肠癌中长链非编码RNA肺癌转移相关转录本1(long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1,lncRNA MALAT1)、miR-200a-3p、PD-L1之间的关系以及其对结肠癌发展的作用,使用实时PCR检测lncRNA MALAT1、miR-200a-3p、PD-L1在结肠癌组织和癌旁正常组织中的表达。通过StarBase和TargetScan数据库预测lncRNA MALAT1、miR-200a-3p、PD-L1之间的结合位点,使用实时PCR和双荧光素酶报告基因试验进一步对其进行验证。通过CCK-8试验、流式细胞术、Transwell试验、划痕试验检测细胞增殖、凋亡、迁移和侵袭情况。结果显示,与癌旁正常组织相比,结肠癌组织lncRNA MALAT1表达显著增多(P<0.001),miR-200a-3p表达显著减少(P<0.001),PD-L1表达显著增多(P<0.05);lncRNA MALAT1与miR-200a-3p相互作用并负向调节其水平(P<0.001)。PD-L1被证实是miR-200a-3p的靶点,并被lncRNA MALAT1间接调控。提示lncRNA MALAT1通过靶向抑制miR-200a-3p促进PD-L1的表达,从而促进结肠癌的增殖、迁移和侵袭。This study was to investigate the expression correlation of long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1(lncRNA MALAT1), miR-200 a-3 p and PD-L1 in colon cancer, and their roles in promoting the progression of colon cancer.The expression levels of lncRNA MALAT1, miR-200 a-3 p and PD-L1 in normal or tumor tissue were determined by real time PCR.StarBase and TargetScan were used for predicting the potential binding sites between lncRNA MALAT1 and miR-200 a-3 p or between miR-200 a-3 p and PD-L1. Real-time PCR and double luciferase reporter genes test were used to further verify the results.CCK-8, flow cytometry, Transwell and scratch test were used to determine proliferation, apoptosis, migration and invasion in vitro. The results showed that comparing with normal tissue, the expression of lncRNA MALAT1 in tumor tissue was significantly increased(P<0.001), while the expression of miR-200 a-3 p was decreased(P<0.001) and the expression of PD-L1 was increased(P<0.05). LncRNA MALAT1 interacted and negatively correlated with miR-200 a-3 p(P<0.001). Further investigations confirmed that PD-L1 was a direct target of miR-200 a-3 p and mediated the effects of lncRNA MALAT1 and miR-200 a-3 p in colon cancer.The above results indicate that lncRNA MALAT1 promotes the progression of colon cancer by modulating miR-200 a-3 p/PD-L1 axis.

关 键 词：结肠癌 长链非编码RNA肺癌转移相关转录本1 微小RNA-200a-3p 程序性死亡受体-配体1 

分 类 号：R392.1[医药卫生—免疫学]