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

Anwar, SL; Wulaningsih, W; Watkins, J; (2017) Profile of the breast cancer susceptibility marker rs4245739 identifies a role for miRNAs. Cancer Biology & Medicine , 14 (4) pp. 387-395. 10.20892/j.issn.2095-3941.2017.0050. Green open access

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Abstract

OBJECTIVE: To determine the influence of the single nucleotide polymorphism (SNP) rs4245739 on the binding and expression ofmicroRNAs and subsequent MDM4 expression and the correlation of these factors with clinical determinants of ER-negativebreast cancers. METHODS: FindTar and miRanda were used to detect the manner in which potential microRNAs are affected by the SNPrs4245739-flanking sequence. RNA sequencing data for ER-negative breast cancer from The Cancer Genome Atlas (TCGA) wereused to compare the expression of miR-184, miR-191, miR-193a, miR-378, and MDM4 in different rs4245739 genotypes. RESULTS: Comparison of ER-negative cancer patients with and without the expression of miR-191 as well as profile microRNAs(miR-184, miR-191, miR-193a and miR-378 altogether) can differentiate the expression of MDM4 among different rs4245739genotypes. Although simple genotyping alone did not reveal significant clinical relationships, the combination of genotyping andmicroRNA profiles was able to significantly differentiate individuals with larger tumor size and lower number of involved lymphnodes (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 region. We demonstrate that the application of these twomethods, in particular the miRNA profile approach, permits detection of new molecular and clinical features related to thers4245739 variant in ER-negative breast cancer.

Type: Article
Title: Profile of the breast cancer susceptibility marker rs4245739 identifies a role for miRNAs
Open access status: An open access version is available from UCL Discovery
DOI: 10.20892/j.issn.2095-3941.2017.0050
Publisher version: http://dx.doi.org/10.20892/j.issn.2095-3941.2017.0...
Language: English
Additional information: Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
Keywords: Rs4245739; ER-negative breast cancer; MDM4; microRNA; clinical relevance
URI: http://discovery.ucl.ac.uk/id/eprint/10043310
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