miR-338-3p在恶性肿瘤中的表达异常及其表观遗传组蛋白的修饰位点  

Dysregulation of miR-338-3p among various malignancies and the histone modification site of epigenetic regulation

作　　者：王文静[1,2] 王晓霏 刘利英 童东东[2] 李茜 倪磊 郭波 WANG Wen-jing;WANG Xiao-fei;LIU Li-ying;TONG Dong-dong;LI Qian;NI Lei;GUO Bo(Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center, Xi'an 710061;Department of Cell Biology and Genetics, Xi'an Jiaotong University Health Science Center, Xi'an 710061;Key Laboratory and Genes Related to Disease, Ministry of Education/Xi'an Jiaotong University Health Science Center, Xi'an 710061, China)

机构地区：[1]西安交通大学第一附属医院肝胆外科,陕西西安710061 [2]西安交通大学医学部细胞生物学与遗传学系,陕西西安710061 [3]西安交通大学医学部环境与疾病相关基因教育部重点实验室,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2019年第5期706-710,721,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省卫生厅科研项目(No.2014D75);陕西省博士后科研项目(No.2016BSHEDZZ90);西安交通大学新教师科研支持计划项目~~

摘　　要：目的探讨不同种类肿瘤中miR-338-3p表达谱及其表达异常的表观遗传修饰调控机制。方法生物信息学大数据库(TCGA Pan-Cancer)分析miR-338-3p在15种不同种类肿瘤组织中的表达谱;以胃癌为研究对象,分析数据库中45例正常胃组织和366例胃癌组织中miR-338-3p表达情况;CRCH37数据库预测miR-338-3p上游启动子区组蛋白修饰位点;利用染色质免疫共沉淀获取组蛋白结合的DNA,PCR扩增miR-338-3p启动子区片段,凝胶电泳验证PCR产物。结果 miR-338-3p在包括食道癌(ESCA)等不同种类肿瘤中表达异常,其中ESCA、头颈部鳞状细胞癌(HNSC)、肾嫌色细胞癌(KICH)、肾乳头状肾细胞癌(KIRP)、肺鳞癌(LUSC)和甲状腺癌(THCA)中表达显著下调(P<0.05),而在结肠腺癌(COAD)、肾透明细胞癌(KIRC)和肝细胞肝癌(LIHC)表达显著上调(P<0.05);366例胃癌组织中miR-338-3p表达普遍下调;染色质免疫共沉淀结合PCR证实组蛋白H3K9m2和H3K4m3是可能引起miR-338-3p下调的两个修饰位点。结论 miR-338-3p在胃癌中表达下调,组蛋白H3K9和H3K4甲基化修饰是潜在原因。Objective To evaluate the expression of miR-338-3p among various types of cancers and investigate the histone modification sites of epigenetics.Methods The data of miR-338-3p expression profile among 15 cancer types were obtained from TCGA Pan-Cancer database (The Cancer Genome Atlas).The expression of miR-338-3p in 45 normal tissues and 366 malignancy tissues of gastric cancer was analyzed.The potential histone modification site in miR-338-3p promoter region was predicated with CRCH37 (Genome Reference Consortium).Chromatin immune coprecipitation (ChIP) and PCR were adopted to detect the modification sites of histone.Results Compared with its counterpart, the miR-338-3p in colon adenocarcinoma, kidney renal clear cell carcinoma and liver hepatocellular carcinoma showed a significantly higher expression ( P <0.05), but a significantly lower one in esophageal carcinoma, head and neck squamous cell carcinoma, kidney chromophobe, kidney renal papillary cell carcinoma, lung squamous cell carcinoma and thyroid carcinoma cancer ( P <0.05).miR-338-3p expression was decreased in 45 normal gastric tissues compared with in 366 gastric cancer tissues.H3K9m2 and H3K4m3 were considered as two potential sites of histone modification of epigenetics which might induce the down-regulation of miR-338-3p in gastric cancer.Conclusion miR-338-3p expression was decreased in gastric cancer and closely associated with two potential sites of histone modification of H3K9m2 and H3K4m3.

关 键 词：miR-338-3p TCGA数据库 染色质免疫共沉淀 组蛋白修饰 表观遗传 

分 类 号：R34[医药卫生—基础医学]