The Role of Non-Coding RNAs in MYC-Mediated Metabolic Regulation: Feedback Loops and Interactions

Metabolic reprogramming is a hallmark of cancer, crucial for supporting the rapid energy demands of tumor cells. MYC, often deregulated and overexpressed, is a key driver of this shift, promoting the Warburg effect by enhancing glycolysis. However, there remains a gap in understanding the mechanisms and factors influencing MYC’s metabolic roles. Recently, non-coding RNAs (ncRNAs) have emerged as important modulators of MYC functions. This review focuses on ncRNAs that regulate MYC-driven metabolism, particularly the Warburg effect. The review categorizes these ncRNA into three main groups based on their interaction with MYC and examines the mechanisms behind these interactions. Additionally, we explore how different types of ncRNAs may collaborate or influence each other’s roles in MYC regulation and metabolic function, aiming to identify biomarkers and synthetic lethality targets to disrupt MYC-driven metabolic reprogramming in cancer. Finaly the review highlights the clinical implications of these ncRNAs, providing an up-to-date summary of their potential roles in cancer prognosis and therapy.With the recent advances in MYC targeted therapy reaching clinical trials the exciting potential of combining these therapies with ncRNA-based strategies holds great promise for enhancing treatment efficacy.