Dysregulation of SIRT1, polyamines and miRNA editing in cancer and aging

Interest in RNA editing has emerged in molecular medicine due to its widespread dysregulation and therapeutic potential. Its regulatory mechanisms in governing non-coding RNAs, especially microRNAs (miRNAs) remain largely unresolved. Emerging evidence in diseases reveals a functional convergence between miRNAs and polyamine metabolism, two systems traditionally studied separately. miRNAs serve as primary substrates for adenosine deaminase acting on RNA (ADAR) which could regulate polyamine metabolism via the sirtuin (SIRT1)-p53 axis, forming a disease-relevant loop. Indeed, in many proliferative malignancies, hyper-editing of miRNAs coincides with high polyamine levels and promotes SIRT1-mediated p53 deacetylation. Conversely, in many age-related diseases, hypo-editing and polyamine loss blunt this pathway. This review dissects this emerging ADAR-editing-miRNA-polyamine circuit anchored on the SIRT1-p53 axis. We propose this as a unifying working model to integrate disparate correlative observations, providing a roadmap for future validation studies to confirm its potential for combinatorial therapeutic targets and diagnostic biomarkers.