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

Michael J.G. Milevskiy, Udai Gujral, Carolina Del Lama Marques, Andrew Stone, Korinne Northwood, Lez J. Burke, Julia M.W. Gee, Kenneth Nephew, Susan Clark, Melissa A. Brown

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)621-632
Number of pages12
JournalBritish Journal of Cancer
Issue number6
StatePublished - Mar 19 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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