| Targeting NAD⁺ Salvage Pathways via Non-Coding RNAs: A Novel Framework for Cancer Understanding and Therapeutic Intervention |
| Paper ID : 1261-IGA |
| Authors |
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Pezhman Shafiei Asheghabadi * Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran |
| Abstract |
| Background and Aim: Nicotinamide adenine dinucleotide (NAD⁺) is a pivotal metabolite and signaling molecule involved in tumor metabolism, cell death regulation, and epigenetic control. This review aims to explore how the NAD⁺ salvage pathway, regulated by non-coding RNAs (ncRNAs), contributes to cancer progression and how it may be targeted for therapeutic interventions. Methods: A comprehensive literature search was conducted using PubMed and Google Scholar, focusing on publications from the past five years. Keywords included “NAD(+)”, “ncRNAs”, “Cancer”, and “Therapeutic Intervention”. Relevant studies investigating the interplay between NAD⁺ metabolism and ncRNAs in cancer were selected for review. Results: NAD⁺ salvage pathways play a key role in regulating ferroptosis, translational control, and cancer stemness. SIRT1, a NAD⁺-dependent deacetylase, enhances ferroptosis in glioma via ATF3 and is regulated by ROS-induced AROS. NMNAT-2-mediated NAD⁺ synthesis supports ribosomal MARylation and proteostasis in ovarian cancer. In colorectal cancer, NFIB promotes NAD⁺ production by inhibiting miR-182-5p’s repression of NAMPT, while SIRT1 reduces miR-1185-1 to promote CD24-mediated stemness. Furthermore, the tumor-suppressive lncRNA MDHDH destabilizes MDH2, altering the NAD⁺/NADH ratio and suppressing glycolysis in glioblastoma. Conclusion: The interaction between NAD⁺ salvage metabolism and ncRNAs offers a novel framework for understanding cancer biology and developing targeted therapies. Modulating this axis, especially via key ncRNAs, holds promise for therapeutic advances across multiple cancer types. |
| Keywords |
| Nicotinamide Adenine Dinucleotide, Non-coding RNAs, Salvage pathways, Therapeutic intervention, Cancer |
| Status: Accepted |
