OBJECTIVETo identify SNPs in the miRNA genes in colorectal cancer (CRC) patients and to investigate their association with CRC.

METHODSDNAs were isolated from 30 CRC tumor tissues and 30 tumor-adjacent tissues, and subjected to target capture using a custom miRNA chip covering 685 miRNA genes from NimbleGen. The captured DNAs were then sequenced using the Illumina's sequencing technology, and the data were analyzed.

RESULTSWe identified 64 SNPs in 43 miRNA genes and most of these SNPs are novel SNPs not reported previously. Prediction of functional consequences of the SNPs using TargetScan and miRSNP showed that SNPs of hsa-mir-1273-G/A, hsa-mir-548h-3-C/U, hsa-mir-1290-A/G, and hsa-mir-1273-C/U resulted in reduction of their mature miRNA abundance. SNPs of hsa-mir-376b-C/G, hsa-mir-604-T/C, hsa-mir-1268-T/G and hsa-mir-146a-C/G resulted in changes in their targeted genes. Finally, we focused on the analysis of SNPs in mir-146a and we found that mir-146a rs1052918 C>G was predicted to promote tumorigenesis via the Wnt signaling pathway.

CONCLUSIONSSNPs in the miRNA genes are important for tumorigenesis. The changes by hsa-mir-146a rs1052918 C>G may result in loss of Wnt, constant activation of the Wnt signaling pathway, and uncontrolled cell proliferation and tumor progression.

Base Sequence ; Cell Proliferation ; Colorectal Neoplasms ; genetics ; pathology ; Humans ; MicroRNAs ; physiology ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA