An Indel Polymorphism within pre-miR3131 Confers Risk for Hepatocellular Carcinoma

Abstract

Polymorphisms in pre-miRNAs may affect its expression, then have effect on its target mRNAs and be associated with cancer susceptibility. In this study, we evaluated the association of an indel polymorphism rs57408770 in pre-miR-3131 with hepatocellular carcinoma (HCC) susceptibility in a Chinese population. The contribution of rs57408770 to HCC risk was investigated in two independent case-control sets (1051 HCC and 1058 controls). Logistic regression analysis showed that the insertion allele of rs57408770 was significantly associated with an increased risk for HCC occurrence in both case-control studies. Moreover, the results of genotype-phenotype correlation analysis from both in vivo and in vitro experiments showed that the insertion allele was significantly correlated with higher expression of mature miR-3131 comparing with the deletion allele. The RNA-Binding Protein Immunoprecipitation assay results indicated that rs57408770 could affect the expression level of mature miR-3131 probably through disturbing the binding of splicing factor SRp20 with pre-miR-3131. Furthermore, overexpression of miR-3131 displayed a proliferation promoting and anti-apoptosis effect on HCC cell lines, suggesting that miR-3131 may act as a proto-oncogene in HCC. Finally, human genome-wide gene expression profile assay was used to screen the targets of miR-3131. The overexpressed miR-3131 could lead to a significant decrease of DTHD1 and XAF1 mRNA level. Taken together, our findings provided evidence that rs57408770 may play a functional role in the carcinogenesis of HCC by affecting SRp20 binding with pre-miR-3131 and affecting the expression of mature miR-3131, subsequently affecting the expression of DTHD1 and XAF1, thus confers risk for HCC.

Evaluation of a 3-base pair indel polymorphism within pre-microRNA-3131 in patients with prostate cancer using mismatch polymerase chain reaction-restriction fragment length polymorphism

“…The present results indicated that the ins/ins genotype of the pre-miR-313 variant significantly increased the risk of PCa. To the best of our knowledge, there has only been one report regarding the impact of a 3-bp indel polymorphism of pre-miR-3131 on cancer risk (20). Wang et al (20) demonstrated that the insertion allele of a 3-bp indel polymorphism of pre-miR-3131 was significantly associated with an increased risk for HCC.…”

“…To the best of our knowledge, there has only been one report regarding the impact of a 3-bp indel polymorphism of pre-miR-3131 on cancer risk (20). Wang et al (20) demonstrated that the insertion allele of a 3-bp indel polymorphism of pre-miR-3131 was significantly associated with an increased risk for HCC. Furthermore, their findings revealed that the 3-bp indel polymorphism could affect the expression level of miR-3131 by influencing the binding of Table II.…”

“…Genotype and allele frequencies of a 3-bp indel (rs57408770) polymorphism of pre-microRNA-3131 in patients with PCa and controls. splicing factor SRp20 with pre-miR-3131 (20). Hsa-miR-3131 is located on chromosome 2 in intron 2 of the Indian hedgehog gene and the 3-bp indel variant (rs57408770) is located in the 3' end of miR-3131 (20).…”

“…Mounting evidence has suggested that mutation or SNPs in miR genes may affect target-binding activity, expression, or processes of mature miR, thus affecting the expression of their target genes (15,16). Polymorphisms in mature and/or pre-miR sequences may affect miR biogenesis and be associated with the development of various types of cancer (17)(18)(19)(20)(21). Small insertions and deletion (indels) polymorphisms are one of the most common genetic alterations in the human genome that influence human traits and diseases (22,23).…”

“…There is limited information regarding the association between pre-miR-3131 polymorphisms and cancer risk. Recently, Wang et al (20) investigated the impact of a 3-bp indel polymorphism (rs57408770) in pre-miR-3131 on hepatocellular carcinoma (HCC) and observed that the insertion (ins) allele significantly increased the risk of HCC in a Chinese population. To the best of our knowledge, for the first time, the present study aimed to determine the impact of a 3-bp indel polymorphism (rs57408770) within pre-miR-3131 on PCa susceptibility in a sample of an Iranian population.…”