Abstract
Noncoding RNAs (ncRNAs) include a diverse range of RNA species, including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs). MiRNAs, ncRNAs of approximately 19–25 nucleotides in length, are involved in gene expression regulation either via degradation or silencing of the messenger RNAs (mRNAs) and have roles in multiple biological processes, including cell proliferation, differentiation, migration, angiogenesis, and apoptosis. LncRNAs, which are longer than 200 nucleotides, comprise one of the largest and most heterogeneous RNA families. LncRNAs can activate or repress gene expression through various mechanisms, acting alone or in combination with miRNAs and other molecules as part of various pathways. Until recently, most research has focused on individual lncRNA and miRNA functions as regulators, and there is limited available data on ncRNA interactions relating to the tumor growth, metastasis, and therapy of cancer, acting either on mRNA alone or as competing endogenous RNA (ceRNA) networks. Triple-negative breast cancer (TNBC) represents approximately 10%–20% of all breast cancers (BCs) and is highly heterogenous and more aggressive than other types of BC, for which current targeted treatment options include hormonotherapy, PARP inhibitors, and immunotherapy; however, no targeted therapies for TNBC are available, partly because of a lack of predictive biomarkers. With advances in proteomics, new evidence has emerged demonstrating the implications of dysregulation of ncRNAs in TNBC etiology. Here, we review the roles of lncRNAs and miRNAs implicated in TNBC, including their interactions and regulatory networks. Our synthesis provides insight into the mechanisms involved in TNBC progression and has potential to aid the discovery of new diagnostic and therapeutic strategies.
Highlights
Triple negative breast cancer (TNBC) represents a heterogeneous subgroup comprising 12%–17% of all of breast cancer (BC) [1]
High expression of miR-95-3p is significantly correlated with decreased overall survival (OS) and relapse-free survival in patients treated with anthracycline-based chemotherapy, and another five-miRNA signature was validated as a novel prognostic and predictive biomarker in Triple-negative breast cancer (TNBC), predicting patient response to anthracycline-based chemotherapy [145]
Decreased levels of miR-200c were only observed in metastatic tumors miR-34c is an independent factor predicting worse prognosis expression of miR-155 is associated with reduced OS (adjusted hazard ratio (HR) = 0.58, 95% confidence interval (CI): 0.34–0.99; crude HR = 0.67, 95% CI: 0.58–0.79)
Summary
Triple negative breast cancer (TNBC) represents a heterogeneous subgroup comprising 12%–17% of all of breast cancer (BC) [1]. MiRNAs are short, single-stranded, ncRNAs (19–25 nucleotides) that account for 1%–5% of the human genome (28,000 mature miRNAs have been identified) and regulate at least 30% of protein-coding genes [18, 19]. They are involved in the regulation of tumor growth, proliferation, differentiation, and apoptosis as oncogenes and tumor suppressors [17, 20].
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