1. CRS4, Science and Technology Park Polaris, Piscina Manna, 09010, Pula, Cagliari, Italy;
2. Department of Clinical and Experimental Medicine, University of Sassari, Viale San Pietro 8, 07100, Sassari, Italy;
3. Department of Diagnostic Services, Pathology Unit, “Giovanni Paolo II” Hospital, ASSL Olbia - ATS Sardegna, Via Bazzoni-Sircana, 07026, Olbia, Italy;
4. Osservatorio Epidemiologico Veterinario Regionale, Via XX Settembre 9, OEVR, 09125, Cagliari, Italy;
5. Department of Biomedical Sciences, University of Sassari, 07100,Viale San Pietro 43b, Sassari, Italy;
6. Department of Pathology, “A. Businco” Oncologic Hospital, ASL Cagliari, Via Jenner 1, 09121, Cagliari, Italy;
7. Istituto di Ricerca Genetica e Biomedica (IRGB), CNR, Cittadella Universitaria di Cagliari, 09042, Monserrato (CA), Italy
*These two authors contributed equally to this work.
The clinical and genetic heterogeneity of Triple Negative Breast Cancer (TNBC) and the lack of unambiguous molecular targets contribute to the inadequacy of current therapeutic options for these variants. MicroRNAs (miRNA) are a class of small highly conserved regulatory endogenous non-coding RNA, which can alter the expression of genes encoding proteins and may play a role in the dysregulation of cellular pathways. Our goal was to improve the knowledge of the molecular pathogenesis of TNBC subgroups analyzing the miRNA expression profile, and to identify new prognostic and predictive biomarkers.
We conducted a human miRNome analysis by TaqMan Low Density Array comparing different TNBC subtypes, defined by immunohistochemical basal markers EGFR and CK5/6. RT-qPCR confirmed differential expression of microRNAs. To inspect the function of the selected targets we perform Gene Ontology and KEGG enrichment analysis.
We identified a single miRNA signature given by miR-135b expression level, which was strictly related to TNBC with basal-like phenotype. miR-135b target analysis revealed a role in the TGF-beta, WNT and ERBB pathways. A significant positive correlation was identified between neoplastic proliferative index and miR-135b expression.
These findings confirm the oncogenic roles of miR-135b in the pathogenesis of TNBC expressing basal markers. A potential negative prognostic role of miR-135b overexpression might be related to the positive correlation with high proliferative index. Our study implies potential clinical applications: miR-135b could be a potential therapeutic target in basal-like TNBCs.
Keywords: Triple Negative Breast Cancer, miR-135b, Basal-like Breast Cancer, Prognostic marker, MicroRNA expression profile, TaqMan Low Density Array