结直肠癌中miR-139-5p与TGIF1的表达及相关性的研究  

Expressions of miR-139-5p and TGIF1 in colorectal cancer and their intercorrelation

作　　者：张丽静[1] 王园园[1] 朱娜娜[1] 董玉娟[2] 贺新奇[1] 赵增仁[1] 

机构地区：[1]河北医科大学第一医院普外科,河北石家庄050031 [2]香港中文大学威尔士亲王医院消化病研究所

出　　处：《肿瘤》2015年第10期1127-1134,共8页Tumor

基　　金：国家自然科学基金资助项目(编号:81072034);河北省自然科学基金资助项目(编号:H2014206313)~~

摘　　要：目的 :检测微RNA(micro RNA,mi RNA,mi R)mi R-139-5p和转化生长因子β-诱导因子1(transforming growth factorβ-induced factor 1,TGIF1)m RNA在结直肠癌中的表达情况,分析二者的关系及其在结直肠发展及预后中可能的作用。方法 :采用实时荧光定量PCR法检测miR-139-5p在44例结直肠癌及其相应癌旁正常组织中的表达情况,通过TargetS can软件预测miR-139-5p的靶基因,并采用实时荧光定量PCR法检测TGIF1 mR NA在44例结直肠癌及其相应癌旁正常组织中的表达情况。在结肠癌HCT116细胞中转染miR-139-5p前体(pre-miR-139),随后采用实时荧光定量PCR和双荧光素酶报告系统鉴定miR-139-5p与TGIF1间的相互作用。统计分析TGIF1 mR NA在结直肠癌组织中的表达情况与结直肠癌患者临床病理特征及预后的相关性。结果 :mi R-139-5p在结直肠癌组织中的表达水平较癌旁正常组织明显降低(P<0.001),而TGIF1 m RNA在癌组织中的表达水平明显高于癌旁正常组织,差异具有统计学意义(P<0.001)。结直肠癌组织中miR-139-5p与TGIF1 mR NA的表达水平呈显著负相关(r=-0.708,P<0.001)。将premiR-139-5p转染结肠癌HCT116细胞后,细胞中miR-139-5p的表达水平显著上调(P<0.001),而TGIF1 mR NA的表达则呈略微下调的趋势(P=0.09)。mi R-139-5p与其靶基因TGIF 1相互作用,TGIF1 m RNA的表达水平与结直肠癌患者肿瘤浸润深度有关,但其表达和患者生存期无关。结论 :mi R-139-5p在结直肠癌组织中表达显著下调,TGIF1 m RNA在结直肠癌中表达显著上调。mi R-139-5p可能通过下调TGIF1的表达,参与了结直肠癌的发展。Objective： To investigate the expression levels of microRNA-139- 5p （miR-139-5p） and transforming growth factor β-induced factor 1（TGIF1） mRNAs in human colorectal cancer （CRC） tissues, and explore their intercorrelation and the role in progression and prognosis of CRC. Methods： The expression levels of miR-139-5p and TGIF1 mRNA in 44 CRC tissue specimens and the corresponding para-cancerous tissues were detected by real-time fluorescent quantitative-PCR. The target gene of rniR-139-5p was predicted by Target Scan software. The colonic cancer HCT116 cells were transfected with pre-miR-139-5p, then the intercorrelation between miR-139-5p and TGIF1 was confirmed by real-time fluorescent quantitative-PCR and DuaI-Luciferase Reporter Assay. The relationships ofTGIF1 mRNA expression with clinicopathological features and prognosis of patients with CRC were analyzed. Results： The expression level of miR-139-5p in CRC tissues was significantly lower than that in the corresponding para-cancerous tissues （P 〈 0.001）, while the expression level of TGIF1 mRNA in CRC tissues was significantly higher than that in the corresponding para-cancerous tissues （P 〈 0.001）. There was a negative correlation between the expression levels of miR- 139-5p and TGIF1 mRNA （r = -0.708, P 〈 0.001）. The expression level of miR-139-5p in HCT116 cells after transfection with pre-miR-139-5p was significantly up-regulated （P 〈 0.001）, while the expression level ofTGIF1 mRNA was down-regulated （P = 0.09）. There was an interaction between miR-139-5p and its target gene TGIF1. The expression of TGIF1 mRNA was correlated with the depth of tumor invasion, but not correlated with the survival. Conclusion： miR-139-5p is down-regulated in human CRC tissues, while TGIF1 mRNA is obviously overexpressed, miR-139-5p may be involved in the development of colorectal cancer through down-regulating the expression of TGIF1.

关 键 词：结直肠肿瘤 微RNA miR-139-5p 转化生长因子 

分 类 号：R735[医药卫生—肿瘤]