Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype
by
, , , ,
Andrea Angius
1,*,†
,
Paolo Cossu-Rocca
2,3,†, 
Caterina Arru
4,
Maria Rosaria Muroni
2,
Vincenzo Rallo
1,4,
Ciriaco Carru
4
,
Paolo Uva
5,
Giovanna Pira
4,
Sandra Orrù
6 and
Maria Rosaria De Miglio
1,* 
1
Institute of Genetic and Biomedical Research (IRGB), CNR, Cittadella Universitaria di Cagliari, 09042 Monserrato, Italy
2
Department of Medical, Surgical and Experimental Sciences, University of Sassari, Via P. Manzella, 4, 07100 Sassari, Italy
3
Department of Diagnostic Services, “Giovanni Paolo II” Hospital, ASSL Olbia-ATS Sardegna, 07026 Olbia, Italy
4
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
5
CRS4, Science and Technology Park Polaris, Piscina Manna, 09010 Pula, CA, Italy
6
Department of Pathology, “A. Businco” Oncologic Hospital, ASL Cagliari, 09121 Cagliari, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2020, 12(11), 3298; https://doi.org/10.3390/cancers12113298
Submission received: 28 September 2020
/
Revised: 5 November 2020
/
Accepted: 5 November 2020
/
Published: 7 November 2020
(This article belongs to the Collection Regulatory and Non-Coding RNAs in Cancer Epigenetic Mechanisms)
Simple Summary
Triple Negative breast cancer (TNBC) is an aggressive tumor showing high histological grade, high recurrence, and frequent metastasis, accounting for about 25% of breast cancer-related deaths. Emerging roles and molecular mechanisms by which miRNAs impact pathogenesis and prognosis of basal-phenotype TNBC and their potential clinical utility are analyzed in the present review. Progress achieved in TNBC molecular taxonomy had minimal clinical impact, while miRNAs could act as prognostic/predictive biomarkers for TNBC subtypes. As there are currently no other therapeutic options to treat TNBC apart from chemotherapy, various studies were reviewed to draw the conclusion that ncRNAs might be candidates for drug development and drug resistance. Targeted approaches to epigenetic mechanisms and clarification of the molecular mechanisms of specific miRNAs in TNBC subtypes are fully justified. This review might provide a collection of biomarkers potentially useful in clinical settings and shows that the combination of miRNA-based therapeutic strategies with conventional therapies might synergize anticancer effects improving patient outcome.
Abstract
Development of new research, classification, and therapeutic options are urgently required due to the fact that TNBC is a heterogeneous malignancy. The expression of high molecular weight cytokeratins identifies a biologically and clinically distinct subgroup of TNBCs with a basal-like phenotype, representing about 75% of TNBCs, while the remaining 25% includes all other intrinsic subtypes. The triple negative phenotype in basal-like breast cancer (BLBC) makes it unresponsive to endocrine therapy, i.e., tamoxifen, aromatase inhibitors, and/or anti-HER2-targeted therapies; for this reason, only chemotherapy can be considered an approach available for systemic treatment even if it shows poor prognosis. Therefore, treatment for these subgroups of patients is a strong challenge for oncologists due to disease heterogeneity and the absence of unambiguous molecular targets. Dysregulation of the cellular miRNAome has been related to huge cellular process deregulations underlying human malignancy. Consequently, epigenetics is a field of great promise in cancer research. Increasing evidence suggests that specific miRNA clusters/signatures might be of clinical utility in TNBCs with basal-like phenotype. The epigenetic mechanisms behind tumorigenesis enable progress in the treatment, diagnosis, and prevention of cancer. This review intends to summarize the epigenetic findings related to miRNAome in TNBCs with basal-like phenotype.
