Dataset Information

Evaluation of polymorphisms in microRNA-binding sites and pancreatic cancer risk in Chinese population.

ABSTRACT: As promising biomarkers and therapy targets, microRNAs (miRNAs) are involved in various physiological and tumorigenic processes. Genetic variants in miRNA-binding sites can lead to dysfunction of miRNAs and contribute to disease. However, systematic investigation of the miRNA-related single nucleotide polymorphisms (SNPs) for pancreatic cancer (PC) risk remains elusive. We performed integrative bioinformatics analyses to select 31 SNPs located in miRNA-target binding sites using the miRNASNP v2.0, a solid database providing miRNA-related SNPs for genetic research, and investigated their associations with risk of PC in two large case-control studies totally including 1847 cases and 5713 controls. We observed that the SNP rs3802266 is significantly associated with increased risk of PC (odds ratio (OR) = 1.21, 95% confidence intervals (CI) = 1.11-1.31, P = 1.29E-05). Following luciferase reporter gene assays show that rs3802266-G creates a stronger binding site for miR-181a-2-3p in 3' untranslated region (3'UTR) of the gene ZHX2. Expression quantitative trait loci (eQTL) analysis suggests that ZHX2 expression is lower in individuals carrying rs3802266-G with increased PC risk. In conclusion, our findings highlight the involvement of miRNA-binding SNPs in PC susceptibility and provide new clues for PC carcinogenesis.

SUBMITTER: Ke J

PROVIDER: S-EPMC7011162 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evaluation of polymorphisms in microRNA-binding sites and pancreatic cancer risk in Chinese population.

Ke Juntao J Peng Xiating X Mei Shufang S Tian Jianbo J Ying Pingting P Yang Nan N Wang Xiaoyang X Zou Danyi D Yang Yang Y Zhu Ying Y Gong Yajie Y Gong Jing J Zhong Rong R Chang Jiang J Fang Zemin Z Miao Xiaoping X

Journal of cellular and molecular medicine 20191227 3

As promising biomarkers and therapy targets, microRNAs (miRNAs) are involved in various physiological and tumorigenic processes. Genetic variants in miRNA-binding sites can lead to dysfunction of miRNAs and contribute to disease. However, systematic investigation of the miRNA-related single nucleotide polymorphisms (SNPs) for pancreatic cancer (PC) risk remains elusive. We performed integrative bioinformatics analyses to select 31 SNPs located in miRNA-target binding sites using the miRNASNP v2. ...[more]

PMID: 31880394

Similar Datasets

Project description:BACKGROUND: MicroRNA dysregulation is a common event in leukemia. Polymorphisms in microRNA-binding sites (miRSNPs) in target genes may alter the strength of microRNA interaction with target transcripts thereby affecting protein levels. In this study we aimed at identifying miRSNPs associated with leukemia risk and assessing impact of these miRSNPs on miRNA binding to target transcripts. METHODS: We analyzed with specialized algorithms the 3' untranslated regions of 137 leukemia-associated genes and identified 111 putative miRSNPs, of which 10 were chosen for further investigation. We genotyped patients with acute myeloid leukemia (AML, n?=?87), chronic myeloid leukemia (CML, n?=?140), childhood acute lymphoblastic leukemia (ALL, n?=?101) and healthy controls (n?=?471). Association between SNPs and leukemia risk was calculated by estimating odds ratios in the multivariate logistic regression analysis. For miRSNPs that were associated with leukemia risk we performed luciferase reporter assays to examine whether they influence miRNA binding. RESULTS: Here we show that variant alleles of TLX1_rs2742038 and ETV6_rs1573613 were associated with increased risk of childhood ALL (OR (95% CI)?=?3.97 (1.43-11.02) and 1.9 (1.16-3.11), respectively), while PML_rs9479 was associated with decreased ALL risk (OR?=?0.55 (0.36-0.86). In adult myeloid leukemias we found significant associations between the variant allele of PML_rs9479 and decreased AML risk (OR?=?0.61 (0.38-0.97), and between variant alleles of IRF8_ rs10514611 and ARHGAP26_rs187729 and increased CML risk (OR?=?2.4 (1.12-5.15) and 1.63 (1.07-2.47), respectively). Moreover, we observed a significant trend for an increasing ALL and CML risk with the growing number of risk genotypes with OR?=?13.91 (4.38-44.11) for carriers of ?3 risk genotypes in ALL and OR?=?4.9 (1.27-18.85) for carriers of 2 risk genotypes in CML. Luciferase reporter assays revealed that the C allele of ARHGAP26_rs187729 creates an illegitimate binding site for miR-18a-3p, while the A allele of PML_rs9479 enhances binding of miR-510-5p and the C allele of ETV6_rs1573613 weakens binding of miR-34c-5p and miR-449b-5p. CONCLUSIONS: Our study implicates that microRNA-binding site polymorphisms modulate leukemia risk by interfering with the miRNA-mediated regulation. Our findings underscore the significance of variability in 3' untranslated regions in leukemia.

Dataset Information

Evaluation of polymorphisms in microRNA-binding sites and pancreatic cancer risk in Chinese population.

Publications

Evaluation of polymorphisms in microRNA-binding sites and pancreatic cancer risk in Chinese population.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets