Genomic Alterations Affecting Competitive Endogenous RNAs (ceRNAs) and Regulatory Networks (ceRNETs) with Clinical Implications in Triple-Negative Breast Cancer (TNBC)

Abstract

The concept of competitive endogenous RNA regulation has brought on a change in the way we think about transcriptional regulation by miRNA–mRNA interactions. Rather than the relatively simple idea of miRNAs negatively regulating mRNA transcripts, mRNAs and other non-coding RNAs can regulate miRNAs and, therefore, broad networks of gene products through competitive interactions. While this concept is not new, its significant roles in and implications on cancer have just recently come to light. The field is now ripe for the extrapolation of technologies with a substantial clinical impact on cancer. With the majority of the genome consisting of non-coding regions encoding regulatory RNAs, genomic alterations in cancer have considerable effects on these networks that have been previously unappreciated. Triple-negative breast cancer (TNBC) is characterized by high mutational burden, genomic instability and heterogeneity, making this aggressive breast cancer subtype particularly relevant to these changes. In the past few years, much has been learned about the roles of competitive endogenous RNA network regulation in tumorigenesis, disease progression and drug response in triple-negative breast cancer. In this review, we present a comprehensive view of the new knowledge and future perspectives on competitive endogenous RNA networks affected by genomic alterations in triple-negative breast cancer. An overview of the competitive endogenous RNA (ceRNA) hypothesis and its bearing on cellular function and disease is provided, followed by a thorough review of the literature surrounding key competitive endogenous RNAs in triple-negative breast cancer, the genomic alterations affecting them, key disease-relevant molecular and functional pathways regulated by them and the clinical implications and significance of their dysregulation. New knowledge of the roles of these regulatory mechanisms and the current acceleration of research in the field promises to generate insights into the diagnosis, classification and treatment of triple-negative breast cancer through the elucidation of new molecular mechanisms, therapeutic targets and biomarkers.