miR-6867及其宿主基因RAPGEFL1在食管鳞状细胞癌组织和细胞系中的表达及甲基化状态

发布时间：2018-05-24 18:14

本文选题：食管鳞状细胞癌 + Rap型鸟苷酸交换因子基因　；参考：《中国肿瘤生物治疗杂志》2017年10期

【摘要】：目的:检测miR-6867及其宿主基因Rap型鸟苷酸交换因子1(rap guanine nucleotide exchange factor like 1,RAPGEFL1)在食管癌细胞系及食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)组织中的表达水平及甲基化状态,并探讨其在ESCC发生发展中的作用。方法:选取河北医科大学第四医院2014年1月至2016年1月收治的ESCC手术患者组织标本87例。应用实时荧光定量PCR(qRT-PCR)检测miR-6867及RAPGEFL1在食管癌细胞系和ESCC组织及其相应癌旁组织中的表达水平,分析miR-6867和RAPGEFL1基因表达之间的相关性。应用甲基化特异性PCR法(MSP)检测RAPGEFL1在食管癌细胞系和ESCC组织及其相应癌旁组织中的甲基化状态。结果:miR-6867在ESCC组织中的相对表达量显著低于其相应癌旁组织(P0.05),并与淋巴结转移及TNM分期有关(P0.05);RAPGEFL1基因在ESCC组织中的表达显著低于其相应癌旁组织(P0.05),并与淋巴结转移、组织分化程度及TNM分期相关(P0.05);miR-6867与RAPGEFL1在ESCC组织中的表达呈明显正相关(P0.05)。5-氮杂-2'-脱氧胞苷(5-Aza-2'-deoxycytidine,5-Aza-dC)处理后,4种食管癌细胞系中miR-6867和RAPGEFL1基因的表达均增高,并且其甲基化程度明显降低。RAPGEFL1基因在ESCC组织中的甲基化率显著高于其相应癌旁组织(P0.05),并与淋巴结转移、组织分化程度及TNM分期有关(P0.05)。结论:ESCC的发生发展可能与miR-6867和RAPGEFL1的异常低表达及RAPGEFL1高甲基化状态有关,miR-6867与RAPGEFL1表达具有一致性,且RAPGEFL1基因启动子区甲基化可能是导致miR-6867与RAPGEFL1表达沉默的机制之一。
[Abstract]:Objective: to detect the expression level and methylation status of miR-6867 and its host gene Rap type guanosine exchange factor 1 (RAP guanine nucleotide exchange factor like 1, RAPGEFL1) in esophageal carcinoma cell lines and esophageal squamous cell carcinoma (esophageal squamous cell), and to explore its role in the development of esophageal squamous cell carcinoma. Methods: 87 cases of ESCC operation in the fourth hospital of Hebei Medical University were selected from January 2014 to January 2016. The expression of miR-6867 and RAPGEFL1 in esophageal cancer cell lines and ESCC tissues and their adjacent tissues were detected by real time fluorescence quantitative PCR (qRT-PCR), and the correlation between the expression of miR-6867 and RAPGEFL1 gene was analyzed. Using methylation specific PCR (MSP) to detect the methylation status of RAPGEFL1 in esophageal cancer cell lines and ESCC tissues and their corresponding para cancerous tissues. Results: the relative expression of miR-6867 in ESCC tissues is significantly lower than that of the corresponding para cancerous tissue (P0.05), and is associated with lymph node metastasis and TNM staging (P0.05); RAPGEFL1 gene is in ESCC tissue. The expression in the medium was significantly lower than that of its corresponding paracancerous tissue (P0.05), which was associated with lymph node metastasis, the degree of tissue differentiation and TNM staging (P0.05); miR-6867 and RAPGEFL1 were positively correlated with the expression of ESCC (P0.05).5- nitrogen heterozygous deoxycytidine (5-Aza-2'-deoxycytidine, 5-Aza-dC), and 4 types of esophageal cancer cell lines The expression of 1 gene increased, and the methylation degree obviously decreased the methylation rate of.RAPGEFL1 gene in ESCC tissue significantly higher than that of its corresponding para cancerous tissue (P0.05), and was associated with lymph node metastasis, the degree of tissue differentiation and TNM staging (P0.05). Conclusion: the occurrence of ESCC may be associated with abnormal low expression of miR-6867 and RAPGEFL1 and RAPGEFL1. The state of hypermethylation is related to the expression of miR-6867 and RAPGEFL1, and methylation of the promoter region of the RAPGEFL1 gene may be one of the mechanisms that lead to the silence of the expression of miR-6867 and RAPGEFL1.
【作者单位】：河北医科大学第四医院河北省肿瘤研究所病理实验室;
【基金】：国家自然科学基金资助项目(No.81572441) 河北省医学科学研究重点课题资助项目(No.20170701,No.20170700)~~
【分类号】：R735.1

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