Non-Coding RNAs Modulating Estrogen Signaling and Response to Endocrine Therapy in Breast Cancer

SIMPLE SUMMARY: Endocrine therapy is a common treatment for estrogen-responsive breast cancer, which is used to block the tumor growth-promoting effect of this hormone. The resistance of breast cancer patients to endocrine therapy is a major clinical problem which could be solved by a deeper understanding of its mechanisms. Analysis of the human genome has revealed that messenger RNA (mRNA) coding for proteins represents only a small portion of human RNA. The vast majority of RNAs do not code for proteins and thus are called non-coding RNAs (ncRNAs), which have important functions in health and disease. Here, we summarize current insights into the effects of ncRNAs on estrogen actions in breast cancer cells and their role in endocrine resistance. NcRNAs have been identified which affect the estrogen response and reduce the efficacy of this therapy. Thus, these could be used to predict therapy response and might represent novel therapy targets to overcome endocrine resistance. ABSTRACT: The largest part of human DNA is transcribed into RNA that does not code for proteins. These non-coding RNAs (ncRNAs) are key regulators of protein-coding gene expression and have been shown to play important roles in health, disease and therapy response. Today, endocrine therapy of ERα-positive breast cancer (BC) is a successful treatment approach, but resistance to this therapy is a major clinical problem. Therefore, a deeper understanding of resistance mechanisms is important to overcome this resistance. An increasing amount of evidence demonstrate that ncRNAs affect the response to endocrine therapy. Thus, ncRNAs are considered versatile biomarkers to predict or monitor therapy response. In this review article, we intend to give a summary and update on the effects of microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) on estrogen signaling in BC cells, this pathway being the target of endocrine therapy, and their role in therapy resistance. For this purpose, we reviewed articles on these topics listed in the PubMed database. Finally, we provide an assessment regarding the clinical use of these ncRNA types, particularly their circulating forms, as predictive BC biomarkers and their potential role as therapy targets to overcome endocrine resistance.