UMMS Affiliation
Horae Gene Therapy Center
Publication Date
2019-09-03
Document Type
Article
Disciplines
Analytical, Diagnostic and Therapeutic Techniques and Equipment | Biological Factors | Cancer Biology | Genetic Phenomena | Neoplasms | Nucleic Acids, Nucleotides, and Nucleosides
Abstract
Breast cancer manifests as a spectrum of subtypes with distinct molecular signatures, and different responses to treatment. Of these subtypes, triple-negative breast cancer (TNBC) has the worst prognoses and limited therapeutic options. Here we report aberrant expression of microRNA-138 (miR-138) in TNBC. Increased miR-138 expression is highly specific to this subtype, correlates with poor prognosis in patients, and is functionally relevant to cancer progression. Our findings establish miR-138 as a specific diagnostic and prognostic biomarker for TNBC. OncomiR-138 is pro-survival; sequence-specific miR-138 inhibition blocks proliferation, promotes apoptosis and inhibits tumour growth in-vivo. miR-138 directly targets a suite of pro-apoptotic and tumour suppressive genes, including tumour suppressor candidate 2 (TUSC2). miR-138 silences TUSC2 by binding to a unique 5'-UTR target-site, which overlaps with the translation start-site of the transcript. Over-expression of TUSC2 mimics the phenotype of miR-138 knockdown and functional rescue experiments confirm that TUSC2 is a direct downstream target of miR-138. Our report of miR-138 as an oncogenic driver in TNBC, positions it as a viable target for oligonucleotide therapeutics and we envision the potential value of using antimiR-138 as an adjuvant therapy to alleviate this therapeutically intractable cancer.
Keywords
Breast cancer, miRNAs
Rights and Permissions
Copyright © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
10.1038/s41598-019-49155-4
Source
Sci Rep. 2019 Sep 3;9(1):12718. doi: 10.1038/s41598-019-49155-4. Link to article on publisher's site
Journal/Book/Conference Title
Scientific reports
Related Resources
PubMed ID
31481748
Repository Citation
Nama S, Muhuri M, Di Pascale F, Quah S, Aswad L, Fullwood M, Sampath P. (2019). MicroRNA-138 is a Prognostic Biomarker for Triple-Negative Breast Cancer and Promotes Tumorigenesis via TUSC2 repression. Open Access Articles. https://doi.org/10.1038/s41598-019-49155-4. Retrieved from https://escholarship.umassmed.edu/oapubs/4003
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons, Biological Factors Commons, Cancer Biology Commons, Genetic Phenomena Commons, Neoplasms Commons, Nucleic Acids, Nucleotides, and Nucleosides Commons