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Title: MicroRNA-138 is a Prognostic Biomarker for Triple-Negative Breast Cancer and Promotes Tumorigenesis via TUSC2 repression
Authors: Nama, S.
Muhuri, M.
Di Pascale, F.
Quah, S.
Aswad, L. 
Fullwood, M. 
Sampath, P. 
Issue Date: 2019
Publisher: Nature Publishing Group
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. Scientific Reports 9 (1) : 12718. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
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. © 2019, The Author(s).
Source Title: Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/s41598-019-49155-4
Rights: Attribution 4.0 International
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