The Pleiotropic Role of the MicroRNA-17-92 Cluster in Cardiovascular Diseases and Cancer.

Abstract

Cardiovascular diseases, including acute myocardial infarctions, heart failure, hypertension, adverse cardiac remodeling, hypertrophy, atherosclerosis, and coronary artery disease, continue to lead to global mortality rates. Annual global cancer mortality rates follow closely behind, emphasizing the need to develop novel therapeutic approaches. MicroRNAs (miRNAs), a class of short non-coding RNAs, regulate cascades of signaling pathways and their downstream targets, exerting control over numerous biological processes. Dysregulation in specific miRNAs is linked to various pathogenesis, including cancer and cardiovascular disease. Among these miRNAs, the miRNA-17-92 cluster plays versatile roles at the nexus of critical physiological and pathological processes, including cardiac diseases and malignancy. This review aimed to provide a holistic analysis of the current progress in identifying, developing, and utilizing the miRNA-17-92 cluster to combat cardiovascular diseases and cancer. The members of the miRNA-17-92 cluster exert control over numerous cellular pathways that regulate, suppress, and promote various aspects of cardiomyocyte differentiation, regeneration, and aging. Certain pathways controlled by the cluster are protective when properly expressed. Others can propagate unchecked cardiovascular disease progression and mortality due to poorly controlled over/under-regulation. Similarly, the miRNA-17-92 cluster plays critical regulatory roles in the occurrence, metastasis, and prognosis of multiple cancers, which may allow the cluster to serve as diagnostic and prognostic biomarkers of malignancy. This review provides a brief overview of the multifaceted roles of the miRNA-17-92 cluster to deliver some insight into the development of novel targeted therapeutics for cardiovascular diseases and cancer via controlling the expression of specific subsets within this cluster. Additionally, this review systematically summarizes the established molecular mechanisms of the miRNA-17-92 cluster and its therapeutic potential in dual pathological contexts, cardiovascular diseases, and cancer.