Functional variants at the miRNA binding sites of the E2F1 gene and its mRNA expression

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.