Target-resequencing to identify microRNA-associated SNP and predict the effect of SNP on microRNA function in colorectal cancer patients
10.3760/cma.j.issn.0253-3766.2015.10.009
- VernacularTitle:结直肠癌患者二代测序鉴定微小RNA单核苷酸多态性位点及其对微小RNA功能的影响
- Author:
Qingchong QIU
1
;
Jie LIU
;
Jiaofang SHAO
;
Xiaoyan LOU
;
Chen CHEN
;
Biaoyang LIN
Author Information
1. 浙江大学浙江加州国际纳米技术研究院系统生物学平台
- Keywords:
Colorectal neoplasms;
MicroRNAs;
Polymorphism,single nucleotide
- From:
Chinese Journal of Oncology
2015;(10):759-763
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify SNPs in the miRNA genes in colorectal cancer ( CRC) patients and to investigate their association with CRC. Methods DNAs 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. Results We 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. Conclusions SNPs 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.