lne—AC079612．1．1—1：1参与结肠癌肝转移的机制研究  

Mechanism of lnc-AC079612.1.1-1：1 in hepatic metastasis of colon cancer

作　　者：沈凯[1] 王杉[1] 叶颖江[1] 姜可伟[1] 申占龙[1] 王搏[1] 张威 Zhang Wei;Wang Bo;Shen Zhanlong;Jiang Kewei;Ye Yingjiang;Wang Shan;Shen Kai(Department of Gastroenterological Surgery,Peking University People＇s Hospital,Laboratory of Surgical Oncology,Peking University People＇s Hospital,Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research,Peking University People＇s Hospital,Beijing 100044,China)

机构地区：[1]北京大学人民医院胃肠外科外科肿瘤研究室结直肠癌诊疗研究北京市重点实验室,100044

出　　处：《国际外科学杂志》2018年第8期523-528,F0004,共7页International Journal of Surgery

基　　金：国家自然科学基金（81702354）;北京大学人民医院研究与发展基金（RDY2016-28）

摘　　要：目的探索lnc-AC079612．1．1—1：1通过靶向调控miR一1915参与结肠癌肝转移的机制，为寻找新的结肠癌治疗靶点提供理论依据。方法连续选取3例同时性结肠癌肝转移患者的肿瘤原发灶和肝转移灶，通过博奥晶芯LncRNA＋mRNA Human Gene Expression Microarray V4．0，4×180K表达谱芯片检测结肠癌原发灶及配对的肝转移灶中lncRNA的表达谱情况，并通过lncRNA表达谱芯片检测，筛选可能与结肠癌肝转移密切相关的lncRNA，然后通过回顾文献对lncRNA的共表达编码基因进行初步分析，以发现可能在结肠癌肝转移过程中起关键作用的lncRNA；通过CCK．8实验，在结肠癌SW480细胞系和SW620细胞系中检测lnc-AC079612．1．1-1：1对结肠癌细胞系增殖能力的影响；通过Transwell细胞侵袭实验，检测lnc—AC079612．1．1．1：1对结肠癌细胞侵袭和转移能力的影响；通过TargetScan、Miranda、incipedia等网站工具，预测可能与lncRNA及MGMT结合的miRNA；双荧光素酶实验验证miR．1915与lnc—AC079612．1．1—1：1的结合作用。采用SPSS22．0统计软件进行数据分析，计量资料以（元±s）表示，两组间比较采用t检验，多组间比较采用F检验。结果肝转移组织与结肠癌原发组织相比，lnc—AC079612．1．1—1：1的表达升高3．94倍，MGMT的表达水平升高3．47倍；共表达分析结果显示，该lncRNA与MGMT基因存在显著共表达关系，共表达相关系数为0．994（P〈0．001）；CCK．8实验发现，过表达lnc—AC079612．1．1．1：1可显著增强结肠癌细胞系SW480和SW620的增殖能力；Transwell细胞侵袭实验发现过表达lnc．AC079612．1．1—1：1，可促进结肠癌细胞系SW480和SW620侵袭和转移能力；通过targetsean、miRanda、lncipedia等网站工具，发现miR一1915—3p是唯一被预测既与lnc—AC079612．1．1-1：1结合，又作用于MGMT的miRNA；双荧光素酶实验发现lnc—AC079612．1．1—1：1与miTo investigate the mechanism of lnc-AC079612.1-1：1 in the metastasis of colorectal cancer by regulating miR-1915 expression and provide a theoretical basis for new therapeutic targets of colon cancer. Methods Continuously harvested 3 pairs of primary tumor and hepatic metastases of patients with synchronous colon cancer with liver metastasis. LncRNA ＋ mRNA Human Gene Expression Microarray V4.0 and 4 x 180K Expression Microarray were used to detect the Expression profile of LneRNA in primary colon cancer and matched liver metastases. The detection of expression profile chip was used to find some ]neRNAs that may be closely associated with colon cancer liver metastasis, and through the literature retrieval, the author preliminarily analyzed the co-expression encoding genes of lneRNAs, in order to find lncRNAs that may play key roles in the process of colon cancer liver metastasis. The effect of lnc-AC079612.1.1-1：1 on the proliferation capacity of colon cancer cell lines was detected in SW480 cell lines and SW620 cell lines of colon cancer through CCK-8 experiment.Effects of lnc-AC079612.1.1-1：1 on the migration and invasion of colon cancer cells were examined by Transwell cell invasion assay. Through TargetScan, Miranda, LNCipedia and other web tools, miRNAs that may bind to IncRNA and o-6-methylguanine-DNA methyl transferase （MGMT） were predicted. Double luciferase reporter gene assay was used to detect the interaction between miR-1915 andlnc-AC079612. 1. 1-1： 1. SPSS 22.0 statistical software was used to analyze the data. The measurement data were expressed as （ ：~ ＋ s ）. T test was compared between the two groups, and multiple groups were compared with F test. Results The expression of lnc- AC079612.1-1：1 was 3.94 times higher in the liver metastases than in the primary tumor, and expression of MGMT was 3.74 times higher in the liver metastases than in the primary tumor. The results showed that there was a significant co-expression relationship between the lncRNA and o-6-methylguanine DN

关 键 词：结肠肿瘤 微RNAS 肿瘤浸润 肝转移 长链非编码RNA 

分 类 号：R73-36[医药卫生—肿瘤]