A Functional Variant At MiR-520a Binding Site In PIK3CA Alters Susceptibility To Colorectal Cancer In A Chinese Han Population

[Objective]An increasing body of evidence has indicated that polymorphisms in the miRNA binding site of target gene can alter the ability of miRNAs to bind their target genes and modulate the risk of cancer. We aimed to investigate the association between a miR-520a binding site polymorphism rs141178472 in the PIK3CA 3’UTR and the risk of colorectal cancer (CRC) in a Chinese Hanpopulation. Genomic DNA was extracted from isolated peripheral blood lymphocytes.[Methods]The study population consisted of 386 cases with CRC confirmed pathologically, and the control subjects in 394 controls were randomly selected from a pool of healthy individuals who got a routine health checkup in age-and sex-matched controls.The PIK3CA rs141178472 was genotyped using the allele-specific PCR assay (AS-PCR). PIK3CA mRNA was detected with the quantitative real-time polymerase chain reaction (qRT-PCR). PIK3CA3’-UTA luciferase reporter plamid (C allele or T allele) constructed and chemically synthesized mature miR-520a were contransfected into 293T cells respectively for further analysis.The polymorphism rs141178472 was analyzed in a case-control study. The relationship between the polymorphism and the risk of colorectal cancer was examined by Statistical methods.[Results]Individuals carrying the rs141178472 CC genotype or C allele had an increased risk of developing CRC (CC vs TT, OR=1.716,95%CI:1.084-2.716, P=0.022; C vs T, OR=1.258,95%CI: 1.021-1.551, P=0.033). Furthermore, the expression of PIK3CA was detected in the peripheral blood mononucleated cell of CRC patients, suggesting that mRNA levels of PIK3CA might be associated with SNP rs141178472.[Conclusion]These findings provide evidence that a miR-520a binding site polymorphism rs141178472 in the PIK3CA 3’ UTR may play crucial roles in the etiology of CRC.