MicroRNAs in regulation of triple-negative breast cancer progression

Abstract

Purpose: Dysregulation of miRNA profile has been associated with a broad spectrum of cellular processes underlying progression of various human malignancies. Increasing evidence suggests that specific microRNA clusters might be of clinical utility, especially in triple-negative breast carcinoma (TNBC), devoid of both predictive markers and potential therapeutic targets. Here we provide a comprehensive review of the existing data on microRNAs in TNBC, their molecular targets, a putative role in invasive progression with a particular emphasis on the epithelial-to-mesenchymal transition (EMT) and acquisition of stem-cell properties (CSC), regarded both as prerequisites for metastasis, and significance for therapy.

Methods: PubMed and Medline databases were systematically searched for the relevant literature. 121 articles have been selected and thoroughly analysed.

Results: Several miRNAs associated with EMT/CSC and invasion were identified as significantly (1) upregulated: miR-10b, miR-21, miR-29, miR-9, miR-221/222, miR-373 or (2) downregulated: miR-145, miR-199a-5p, miR-200 family, miR-203, miR-205 in TNBC. Dysregulation of miR-10b, miR-21, miR-29, miR-145, miR-200 family, miR-203, miR-221/222 was reported of prognostic value in TNBC patients.

Conclusion: Available data suggest that specific microRNA clusters might play an important role in biology of TNBC, understanding of which should assist disease prognostication and therapy.

Keywords: CSC; EMT; Invasion; MicroRNA; Triple-negative breast carcinoma.

Fig. 1

Schematic presentation of microRNAs involvement in regulation of epithelial-to mesenchymal transition (EMT) and acquisition of stem cell-like properties (CSC) in triple-negative breast carcinoma. Red/green arrows—upregulated/downregulated microRNAs; black arrows/truncated lines—activation (upregulation)/repression (inhibition) of signalling pathways