Journal Article

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

Liu, Sen, Ramamonjiharisoa, Miora Bruna Marielle

2026

Overview

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. Graphical abstract The scheme merges correlative data: cancers display high ADAR activity, hyper-edited miRNAs and elevated polyamines, whereas aging shows the opposite trend. Whether these edited miRNAs causally shape polyamine levels via the SIRT1-p53 axis remains experimentally untested. The diagram therefore depicts a working model linking ADAR editing, SIRT1-p53 signaling and polyamine regulators of biosynthesis/autophagy. The solid red arrows trace the primary regulatory axis synthesized from the reviewed evidence (from ADAR to p53, to polyamine), while the dashed green arrows indicate a potential feedback loop from polyamines back to the editing machinery that is currently supported by more limited data

• Publisher: Springer Vienna,Springer Nature B.V,Springer
• Subject: ADAR / Adenosine / Adenosine deaminase / Adenosine Deaminase - genetics / Adenosine Deaminase - metabolism / Age related diseases / Aging / Aging - genetics / Aging - metabolism / Analytical Chemistry / Animals / Autophagy / Biochemical Engineering / Biochemistry / Biomarkers / Biomedical and Life Sciences / Biosynthesis / Cancer / Combinatorial analysis / Cytoplasm / Deacetylation / Editing / Enzymes / Feedback loops / Homeostasis / Humans / Life Sciences / Malignancy / Metabolism / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / miRNA / MiRNA editing / Neoplasms - genetics / Neoplasms - metabolism / Neoplasms - pathology / Neurobiology / P53 / p53 Protein / Polyamines / Polyamines - metabolism / Proteins / Proteomics / Review / Review Article / Ribonucleic acid / RNA / RNA Editing / Senescence / SIRT1 / SIRT1 protein / Sirtuin 1 - genetics / Sirtuin 1 - metabolism / Therapeutic targets / Tumor Suppressor Protein p53 - genetics / Tumor Suppressor Protein p53 - metabolism / Weapons