Noncoding RNAs: potential regulators in cardioncology

Abstract

Cancer is the leading cause of morbidity and mortality in the United States and globally. Owing to improved early diagnosis and advances in oncological therapeutic options, the number of cancer survivors has steadily increased. Such efficient cancer therapies have also lead to alarming increase in cardiovascular complications in a significant proportion of cancer survivors, due to adverse cardiovascular effects such as cardiotoxicity, cardiac atrophy, and myocarditis. This has emerged as a notable concern in healthcare and given rise to the new field of cardioncology, which aims at understanding the processes that occur in the two distinct disorders and how they interact to influence the progression of each other. A key player in both cancer and heart failure is the genome, which is predominantly transcribed to noncoding RNAs (ncRNAs). Since the emergence of ncRNAs as master regulators of gene expression, several reports have shown the relevance of ncRNAs in cancer and cardiovascular disorders. However, the knowledge is quite limited regarding the relevance of ncRNAs in cardioncology. The objective of this review is to summarize the current knowledge of ncRNAs in the context of cardioncology. Furthermore, the therapeutic strategies as well as the prospective translational applications of these ncRNA molecules to the clinics are also discussed.

Keywords: biomarker; cardiotoxicity; doxorubicin; heart failure; noncoding RNA.

Fig. 1.

Overview of cardiotoxicity induced by cancer treatment. There are several therapeutic strategies used for treatment of cancer (left). In particular, chemotherapy treatment with anthracyclines can be accompanied by detrimental toxic effects on the cardiovascular system of patients leading to cardiac dysfunction (right). Cellular and pathological consequences are highlighted in green and yellow, respectively.

Fig. 2.

Noncoding RNA (ncRNA)-based diagnostic and therapeutic approaches for cardiotoxicty. ncRNAs [microRNAs (miRNAs; purple), long ncRNAs (lncRNAs; yellow), and circular RNAs (circRNAs; gray)] can be used as novel biomarkers of cancer-induced cardiotoxicity. A few examples of miRNA and lncRNA molecules with reported biomarker and therapeutic potential for cardiotoxicity have been highlighted (in bold), whereas the predicted therapeutic molecules (not in bold) are symbolized with a question mark. Furthermore, ncRNAs are potential therapeutic targets. Unique antisense chemistries or the noncoding sequence itself may be delivered via viral particles, via nanoparticles, or through injection of the free molecule into the cardiomyocytes of vascular system. The strategy is to silence or activate the endogenous ncRNAs.