XAF1转录变异体在结直肠肿瘤中的差异表达

Differential Expression of Transcriptional Variants of XAF1 in Colorectal Neoplasms

背景:X连锁凋亡抑制蛋白(XIAP)相关因子1(XAF1)能与XIAP结合而拮抗其caspase抑制活性,从而促进细胞凋亡,已被认定是一种肿瘤抑制基因。在多种肿瘤细胞中可检测到XAF1转录变异体,但不同转录变异体在结直肠肿瘤中的表达情况尚不明确。目的:检测XAF1及其转录变异体在不同结直肠组织中的表达,初步探讨其在结直肠肿瘤发生、发展中的作用。方法:收集结直肠癌及其配对癌旁组织、增生性息肉、腺瘤和正常结直肠黏膜组织样本,以免疫组化法和蛋白质印迹法检测XAF1蛋白表达,RT-PCR检测XAF1转录变异体表达。结果:与正常结直肠黏膜相比,XAF1蛋白在增生性息肉、腺瘤和癌组织中的胞核表达强度显著降低(P<0.05),胞质表达强度有所增高(P>0.05),总体表达强度显著降低(P<0.05)。结直肠癌组织中的XAF1A蛋白表达显著低于相应癌旁组织(P<0.05)。转录变异体XAF1A、XAF1B、XAF1C mRNA在结直肠肿瘤中的表达均显著低于正常结直肠黏膜(P<0.05)。结论:XAF1及其转录变异体在结直肠肿瘤和正常结直肠黏膜中存在差异表达,腺瘤阶段即已出现XAF1表达下降并由胞核向胞质易位。转录后修饰可能影响XAF1基因功能。

Background： The tumor suppressor,X-linked inhibitor of apoptosis（ XIAP）-associated factor 1（ XAF1） is a XIAPbinding protein that antagonizes the anti-caspase activity of XIAP,thereby enhancing apoptosis. Transcriptional variants of XAF1 have been detected in various tumor cells,however,the expression profile of these transcriptional variants in colorectal neoplasms remains unclear. Aims： To investigate the expressions of XAF1 and its transcriptional variants in different colorectal tissues and their roles in tumorigenesis and development of colorectal neoplasms. Methods： Samples of colorectal cancer and paired adjacent tissue,hyperplastic polyp,adenomatous polyp,and normal colorectal mucosa were collected from surgical operation or endoscopic biopsies. XAF1 protein expression was detected by immunohistochemistry and Western blotting,and the transcriptional variants of XAF1 were detected by RT-PCR. Results： Compared with normal colorectal mucosa,the expression level of XAF1 protein in nucleus was significantly reduced（ P〈0. 05） and that in cytoplasm was slightly increased（ P〈0. 05） in hyperplastic polyp,adenomatous polyp,and cancerous tissue,and the overall expression level of XAF1 protein was decreased（ P〈0. 05）. XAF1 A protein expression in cancerous tissue was significantly reduced when compared with the paired adjacent tissue（ P〈0. 05）. mRNA expressions of three transcriptional variants of XAF1,XAF1 A,XAF1B and XAF1 C were all significantly lower in neoplastic tissues than in normal mucosa（ P〈0. 05）.Conclusions： XAF1 and its transcriptional variants are differentially expressed in colorectal neoplasms and normal colorectal mucosa. These changes occurred initially in adenomatous polyp accompanied by a redistribution of XAF1 from nucleus to cytoplasm. Post-transcriptional modification may affect XAF1 gene function.