miR-192与ZEB2在结直肠癌中的表达及其临床意义

The expression and clinical significance of microRNA-192 and ZEB2 in colorectal cancer

背景与目的:微小RNA(microRNA,miRNA)是一类具有重要调控作用的非编码小分子RNA,在多种疾病的发生、发展中起重要作用。本研究通过检测结直肠癌(colorectal cancer,CRC)组织中miR-192及E盒结合锌指蛋白2(zinc finger E-box binding homeobox 2,ZEB2)mRNA、蛋白表达,分析miR-192的异常表达与CRC的临床病理特征的关系及与ZEB2的相关性。方法:选择CRC组织和癌旁组织(距肿瘤边缘≥5 cm)各30例,结直肠腺瘤组织25例,正常结直肠组织15例。实时定量PCR(quantitative real-time polymerase chain reation,qRT-PCR)法检测上述各组中miR-192及ZEB2 mRNA表达;蛋白质印迹法(Western blot)检测ZEB2蛋白表达;对CRC组织中miR-192与临床病理特征关系及前者与ZEB2的相关性进行分析。结果:CRC组miR-192表达明显下调,ZEB2 mRNA和蛋白表达明显上调,分别与癌旁组、结直肠腺瘤组及正常组相比,差异均有统计学意义(P<0.05);miR-192的表达下调与CRC的淋巴结转移(P=0.021)和远处转移(P=0.023)相关。在CRC组织中,miR-192与ZEB2蛋白的表达呈显著的负相关关系(r=-0.365,P<0.05)。结论:miR-192在CRC组织中的表达下调与肿瘤的转移有关,且可能通过ZEB2参与CRC的发生、发展过程。

Background and purpose： MicroRNA（miRNA） is a class of small non-coding RNA playing an important regulatory role in many diseases. In this study, we explore the levels of miR-192 and zinc ifnger E-box binding homeobox 2 （ZEB2） in CRC, the clinical signiifcance of miR-192 and the correlation between the expression of miR-192 and ZEB2 protein. Methods： The expression levels of miR-192 and ZEB2 mRNA in 30 colorectal carcinoma samples, 30 corresponding cancer-adjacent tissue samples （from the edge of tumor≥5 cm）, 25 colorectal adenoma samples, and 15 normal tissue samples were quantiifed using quantitative real-time polymerase chain reaction （qRT-PCR）. ZEB2 protein expression was determined using Western blot. The relationship between the miR-192 and clinicopathological factors, miR-192 and ZEB2 protein expression was analyzed. Results：Signiifcant upregulation of miR-192 expression and reduction of ZEB2 mRNA and protein expression were identiifed in CRC tissues, compared to cancer-adjacent tissues, colorectal adenoma samples, and normal tissues （P〈0.05）. Low miR-192 levels were signiifcantly associated with lymph node （P=0.021） and distant metastasis （P=0.023）. An inverse relationship between miR-192 and ZEB2 protein expression was identified in CRC group （r=-0.365, P〈0.05）. Conclusion： MiR-192 downexpression was correlated with CRC metastasis. MiR-192 may play a role in the development and progression of CRC through ZEB2.