Samidurai Arun, Saravanan Manu, Zwiren Virginia Villani, Kodali Varun, Savsani Kush, Bhuiyan Nuhash, Yerramothu Shruti, Lau Suet Ying Valerie, Baral Ena, Hammel Sara, Das Anindita
Division of Cardiology, Pauley Heart Center, Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Rev Cardiovasc Med. 2025 May 27;26(5):27966. doi: 10.31083/RCM27966. eCollection 2025 May.
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.
心血管疾病,包括急性心肌梗死、心力衰竭、高血压、不良心脏重塑、肥大、动脉粥样硬化和冠状动脉疾病,仍然是全球死亡率的主要原因。全球年度癌症死亡率紧随其后,这凸显了开发新型治疗方法的必要性。微小RNA(miRNA)是一类短的非编码RNA,可调节信号通路及其下游靶点的级联反应,从而控制众多生物学过程。特定miRNA的失调与包括癌症和心血管疾病在内的各种发病机制有关。在这些miRNA中,miRNA-17-92簇在包括心脏病和恶性肿瘤在内的关键生理和病理过程的交汇处发挥着多种作用。本综述旨在全面分析在识别、开发和利用miRNA-17-92簇来对抗心血管疾病和癌症方面的当前进展。miRNA-17-92簇的成员控制着众多细胞通路,这些通路调节、抑制和促进心肌细胞分化、再生和衰老的各个方面。该簇控制的某些通路在正常表达时具有保护作用。其他通路可能由于调控过度或不足而导致心血管疾病进展和死亡率不受控制地上升。同样,miRNA-17-92簇在多种癌症的发生、转移和预后中发挥关键调节作用,这可能使该簇成为恶性肿瘤的诊断和预后生物标志物。本综述简要概述了miRNA-17-92簇的多方面作用,以期通过控制该簇内特定亚群的表达,为开发针对心血管疾病和癌症的新型靶向治疗药物提供一些见解。此外,本综述系统地总结了miRNA-17-92簇已确立的分子机制及其在心血管疾病和癌症这两种病理背景下的治疗潜力。