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Profile of the breast cancer susceptibility marker rs4245739 identifies a role for miRNAs

Cancer Biology & Medicine 2017年第4期14卷 387-395页

作者： Sumadi Lukman Anwar Wahyu Wulaningsih johnathan watkins PILAR Research Network Cambridgeshire CB1 2JD UK Division of Surgical Oncology Department of Surgery Faculty of Medicine Universitas Gadjah Mada Yogyakarta 55281 Indonesia Division of Hemato-Oncology Department of Internal Medicine Faculty of Medicine Universitas Gadjah Mada Yogyakarta 55281 Indonesia MRC Unit for Lifelong Nealth and Ageing University College London London WCIB 5JU UK Institute of Molecular and Mathematical Biomedicine King's College London London SE1 1UL UK

Objective:To determine the influence of the single nucleotide polymorphism(SNP)rs4245739 on the binding and expression of micro RNAs and subsequent MDM4 expression and the correlation of these factors with clinical determinants of ER-negative breast ***:Find Tar and miRanda were used to detect the manner in which potential micro RNAs are affected by the SNP rs4245739-flanking *** sequencing data for ER-negative breast cancer from The Cancer Genome Atlas(TCGA)were used to compare the expression of miR-184,miR-191,miR-193a,miR-378,and MDM4 in different rs4245739 ***:Comparison of ER-negative cancer patients with and without the expression of miR-191 as well as profile micro RNAs(miR-184,miR-191,miR-193a and miR-378 altogether)can differentiate the expression of MDM4 among different rs4245739 *** simple genotyping alone did not reveal significant clinical relationships,the combination of genotyping and micro RNA profiles was able to significantly differentiate individuals with larger tumor size and lower number of involved lymph nodes(P<0.05)in the risk group(A allele).Conclusions:We present two novel methods to analyze SNPs within 3′UTRs that use:(i)a single miRNA marker expression and(ii)an expression profile of miRNAs predicted to bind to the SNP *** demonstrate that the application of these two methods,in particular the miRNA profile approach,permits detection of new molecular and clinical features related to the rs4245739 variant in ER-negative breast cancer.

关键词： Rs4245739 ER-negative breast cancer MDM4 microRNA clinical relevance

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