MicroRNA-196a is regulated by ER and is a prognostic biomarker in ER+ breast cancer
| Autor: | Michael J. G. Milevskiy, Carolina Marques, Lez J. Burke, Andrew Stone, Udai Gujral, Melissa A. Brown, Kenneth P. Nephew, Susan J. Clark, Julia Margaret Wendy Gee, Korinne Northwood |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cancer Research
Transcriptional regulatory elements Breast Neoplasms Disease Biology Article 03 medical and health sciences 0302 clinical medicine Breast cancer Cyclin-dependent kinase microRNA medicine Transcriptional regulation Biomarkers Tumor Humans Hox gene Gene 030304 developmental biology Regulation of gene expression Homeodomain Proteins 0303 health sciences Estrogen Receptor alpha Cancer DNA Methylation medicine.disease Prognosis Chromatin 3. Good health Gene Expression Regulation Neoplastic MicroRNAs Tamoxifen Oncology Drug Resistance Neoplasm 030220 oncology & carcinogenesis DNA methylation miRNAs Cancer research biology.protein Disease Progression MCF-7 Cells Female |
| Zdroj: | British Journal of Cancer |
| ISSN: | 0007-0920 |
| Popis: | Background\ud \ud 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.\ud \ud Methods\ud \ud 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.\ud \ud Results\ud \ud 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.\ud \ud Conclusion\ud \ud This work sheds light on the normal and abnormal regulation of MIR196A and provides a novel stratification method for therapeutically resistant breast cancer. |
| Databáze: | OpenAIRE |
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