Objective: Cyclin D1 is an essential protein that acts as a mitogenic sensor. In this manuscript, we discuss the importance of cyclin D1 in oncology and cardio-oncology, and we challenge the prognostic and therapeutic response values of cyclin D1 to figure out if it can be a beneficial marker. We also discuss the agents and microRNAs that can be used as a potential therapeutic approach via regulating cyclin D1 expression in oncology and cardio-oncology. Discussion: Clinical significance of cyclin D1 is defined not only in several cancers such as breast cancer, melanoma, and glioblastoma but also in cardiomyocyte regeneration and cardiac hypertrophic growth. Several studies have indicated that the injection of cardiotoxic agents such as doxorubicin (DOX) induces damage to the cardiac system and increases cyclin D expression at single injection, which might be related to DXO-mediated damage in the adult heart. However, cyclin D1 overexpression leads to hypertrophic growth of cardiomyocytes, and cyclin-dependent kinase (CDK)) inhibitors such as p16 do not inhibit the hypertrophic growth of cardiomyocytes. Thus, the reaction is CDK-independent. Conclusions: Cyclin D1 overexpression is positively correlated with tumor progression, treatment response, cardiotoxicity, and poor prognosis. Cyclin D1 expression has an important role in cardiac hypertrophy, and it can be a promising marker in monitoring cardiomyocyte treatment responses, cardioprotection, and cardiotoxicity. Finally, cyclin D1 plays an important role in hypertrophic growth of cardiomyocytes via a novel mechanism. Given all these pieces of evidence, cyclin D1 can be introduced as a favorable biomarker in future cardiology and cardio-oncology.
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