Functional variants at the miRNA binding sites of the E2F1 gene and its mRNA expression
Functional variants at the miRNA binding sites of the E2F1 gene and its mRNA expression
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E2F1 基因 miRNA 结合位点的功能变异及其 mRNA 表达
DOI：
10.3892/ol.2012.999
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发表时间：
2013-01-01
期刊：
影响因子：
2.9
通讯作者：
Guan, Xiaoxiang
中科院分区：
文献类型：
--
作者：
Zhao, Yunzhao;Tang, Lin;Guan, Xiaoxiang
转录因子E2 F1是细胞增殖和凋亡的关键调节因子，在许多恶性肿瘤中经常发现E2 F1的表达失调。先前的研究已经确定E2 F1基因3非翻译区（3 'UTR）microRNA（miRNA）结合位点变异与癌症风险显著相关;然而，E2 F1基因3' UTR中的遗传变异在其转录后调控中的作用尚未阐明。因此，使用来自HapMap在线数据库的mRNA表达数据，我们分析了E2 F1的miRNA结合位点的变体与其mRNA表达之间的关联。在本研究中，我们报告了5个变体的推定的miRNA结合位点在E2 F1的3 'UTR的生物信息学分析的鉴定。其中，发现rs3213180与来自HapMap数据库的淋巴母细胞系中的E2 F1表达显著相关（P=0.045）;然而，在本研究中，rs3213182（P=0.345）和rs3213183（P=0.402）没有显著相关性。本研究表明，rs3213180可能是一个假定的变异介导的转录后调控E2 F1靶基因。总之，3 'UTR多态性与淋巴母细胞系中E2 F1的表达显著相关。然而，这一发现需要进一步的功能分析，涉及E2 F1转录活性与3 'UTR的变体相关的潜在机制的验证。
The transcription factor E2F1 is a key regulator of cell proliferation and apoptosis, and deregulated expression of E2F1 has been frequently found in a number of malignancies. Previous studies have indentified that E2F1 genetic 3 untranslated region (3'UTR) microRNA (miRNA) binding site variants are significantly associated with cancer risk; however, the roles of genetic variants in the E2F1 3'UTR in its post-transcriptional regulation have not been elucidated. Hence, using mRNA expression data from the HapMap online database, we analyzed the association between the variants at the miRNA binding sites of E2F1 and its mRNA expression. In the present study, we report the identification of 5 variants of putative miRNA binding sites in the E2F1 3'UTR by bioinformatic analysis. Among them, rs3213180 was found to be significantly associated with E2F1 expression in lymphoblastoid cell lines from the HapMap database (P=0.045); however, no significant association was demonstrated in this study for rs3213182 (P=0.345) and rs3213183 (P=0.402). This study demonstrated that rs3213180 may be a putative variant mediating the post-transcriptional regulation of the E2F1 target gene. In conclusion, 3'UTR polymorphism is significantly associated with E2F1 expression in lymphoblastoid cell lines. However, this finding requires validation in further functional analysis of the underlying mechanism involving E2F1 transcriptional activity associated with variants in the 3'UTR.