MicroRNA-138 is a prognostic biomarker for triple-negative breast cancer and promotes tumorigenesis via TUSC2 repression

• Main Authors: Nama, Srikanth, Muhuri, Manish, Di Pascale, Federica, Quah, Shan, Aswad, Luay, Fullwood, Melissa, Sampath, Prabha
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2020
• Subjects: Science::Biological sciences; Breast Cancer; MicroRNA-138
• Online Access: https://hdl.handle.net/10356/142966
• Institution: Nanyang Technological University

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.