食管鳞癌肿瘤微环境中miRNA与TGF-β1的相关性分析  

Correlations between miRNAs and TGF-β1 in tumor microenvironment of esophageal squamous cell cancer

作　　者：朱龙萍[1] 金丽艳[1] 蒋日月[1] 汪茜茜[1] 蒋健[1] 毛朝明[1] 陈德玉[1] 

机构地区：[1]江苏大学附属医院肿瘤研究院,江苏镇江212001

出　　处：《细胞与分子免疫学杂志》2013年第5期524-528,共5页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(30872335)

摘　　要：目的检测mir-18a-5p、mir-23a-3p、mir-24-3p、mir-25-3p和TGF-β1在食管鳞癌(ESCC)患者肿瘤微环境中的表达水平,分析它们在ESCC发生发展中的作用及相互关系。方法收集52例ESCC患者癌组织、癌旁组织手术标本;实时荧光定量PCR检测ECA-109、TE-1细胞株、正常食管上皮细胞和52例ESCC患者手术标本的mir-18a-5p、mir-23a-3p、mir-24-3p、mir-25-3p和TGF-β1的mRNA表达水平;Western blot法检测TGF-β1在上述细胞以及组织中的蛋白表达情况。结果与正常食管上皮细胞相比,mir-18a-5p、mir-24-3p、mir-25-3p、mir-23a-3p在ESCC细胞株ECA-109中的表达明显增高(P<0.05),其中前3种miRNA在ESCC细胞株TE-1的表达明显增高(P<0.05);TGF-β1在ESCC细胞株ECA-109、TE-1中明显低表达(P<0.05)。与癌旁组织对照组相比,52例ESCC患者癌组织标本的mir-18a-5p、mir-23a-3p、mir-24-3p、mir-25-3p显著升高[上调比例分别为86.5%(45/52)、63.5%(33/52)、78.8%(41/52)、86.5%(45/52),P<0.05],TGF-β1显著降低(P<0.05)。ESCC患者mir-18a-5p、mir-23a-3p、mir-24-3p、mir-25-3p的高表达和TGF-β1的低表达与患者性别、年龄、肿瘤大小、肿瘤位置等无明显关系,但mir-18a-5p、mir-23a-3p与患者癌组织分化程度相关,mir-25-3p与患者癌组织分化程度、浸润深度和范围相关(P<0.05)。癌组织中TGF-β1的低表达与患者癌组织分化程度、浸润深度和范围相关(P<0.05)。mir-18a-5p、mir-23a-3p与TGF-β1的表达无相关性,mir-24-3p、mir-25-3p与TGF-β1的表达呈负相关。结论 ESCC肿瘤微环境中mir-18a-5p、mir-23a-3p、mir-24-3p、mir-25-3p和TGF-β1可能在ESCC的发生发展中有一定作用。Objective To detect the levels of mir-18a-Sp, mir-23a-3p, mir-24-3p, mir-25-3p and TGF-I3] in tumor micro- environment of esophageal squamous cell cancer （ESCC） patients and explore their clinical significances and correlations. Methods The mRNA expressions of mir-18a-Sp, mir-23a-3p, mir-24-3p, mir-25-3p and TGF-~! were measured by real-time quantitative RT-PCR in ESCC cell lines ECA-109 and TE-I, normal esophageal squamous epithelial cells, tumor tissues and tumor-adjacent normal tissues from 52 ESCC patients. The expression of TGF-~I protein in the three types of cells, tumor tissues and tumor-adjacent normal tissues from 52 ESCC patients was detected by Western blotting. Results The expres- sions of mir-18a-5p, mir-24-3p, mir-25-3p and mir-23a-3p in ECA-109 were significantly higher than those in normal esophage- al squamous epithelial cells （P〈O.05） ; that is also true of the first three miRNAs in TE-] （P〈O. 05）. Compared with the normal esophageal squamous epithelial cells, the expression of TGF-I31 was reduced in ECA-t09 and TE-] （ P 〈 O. 05 ）. Compared with the normal tissues, ESCC tumor tissues were characterized by significant overexpressions of mir-18a-5 p, mir- 23a-3p, mir-24-3p and mir-25-3p with the rates being 86.5% （45/52）, 63.5% （33/52）, 78.8% （41/52）, 86.5% （45/52）, respectively （ all P 〈 0.05）, and by significantly decreased expression of TGF-13] （ P 〈 0.05 ）. The up-regulation of mira 8a- 5p, mir-23a-3p, mir-24-3p, mir-25-3p and the down-regulation of TGF-{}I were not correlated with sex, age, tumor size and tumor site in ESCC patients, but the overexpressions of mir-18a-Sp, mir-23a-3p, mir-25-3p were significantly related to tumor differentiation （P 〈 O. 05）, and a significant variation of mir-25-3p was found in different T stages （P 〈 O. 05 ）. TGF-131 level was lower in tumor tissues compared to normal tissues from the 5 2 ESCC patients, and higher in stage T=/~ than stage T I/II （P〈0.05）, and a significant variation was foun

关 键 词：微小RNA TGF-Β1 食管鳞状细胞癌 

分 类 号：R392.33[医药卫生—免疫学] R730.3[医药卫生—基础医学]