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MicroRNA-196a is regulated by ER and is a prognostic biomarker in ER+ breast cancer

Milevskiy, Michael J. G., Gujral, Udai, Del Lama Marques, Carolina, Stone, Andrew, Northwood, Korinne, Burke, Lez J., Gee, Julia M. W., Nephew, Kenneth, Clark, Susan and Brown, Melissa A. 2019. MicroRNA-196a is regulated by ER and is a prognostic biomarker in ER+ breast cancer. British Journal of Cancer 120 , pp. 621-632. 10.1038/s41416-019-0395-8

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Abstract

Background MicroRNAs are potent post-transcriptional regulators involved in all hallmarks of cancer. Mir-196a is transcribed from two loci and has been implicated in a wide range of developmental and pathogenic processes, with targets including Hox, Fox, Cdk inhibitors and annexins. Genetic variants and altered expression of MIR196A are associated with risk and progression of multiple cancers including breast cancer, however little is known about the regulation of the genes encoding this miRNA, nor the impact of variants therein. Methods Genomic data and chromatin interaction analysis were used to discover functional promoter and enhancer elements for MIR196A. Expression data were used to associate MIR196A with mechanisms of resistance, breast cancer subtypes and prognosis. Results Here we demonstrate that MIR196A displays complex and dynamic expression patterns, in part controlled by long-range transcriptional regulation between promoter and enhancer elements bound by ERα. Expression of this miRNA is significantly increased in drug-resistant models of hormone-receptor positive disease. The expression of MIR196A also proves to be a robust prognostic factor for patients with advanced and post-menopausal ER+ disease. Conclusion This work sheds light on the normal and abnormal regulation of MIR196A and provides a novel stratification method for therapeutically resistant breast cancer.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Publisher: Nature Publishing Group
ISSN: 0007-0920
Date of First Compliant Deposit: 22 February 2019
Date of Acceptance: 15 January 2019
Last Modified: 16 Apr 2019 14:04
URI: http://orca-mwe.cf.ac.uk/id/eprint/119805

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