MicroRNA Regulation of SIRT1.pdfVIP

REVIEW ARTICLE published: 30 March 2012 doi: 10.3389/fphys.2012.00068 MicroRNA regulation of SIRT1 MunekazuYamakuchi* Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA Edited by: YuWang, The University of Hong Kong, Hong Kong Reviewed by: Sanjukta Chakraborty, Texas AM Health Science Center, USA Jon Andresen, University of Missouri-Kansas City, USA *Correspondence: MunekazuYamakuchi , Department of Medicine, Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box CVRI, Rochester, NY 14642, USA. e-mail: munekazu_yamakuchi@urmc. SIRT1 is an NAD-dependent deacetylase that regulates stress response pathways. By deacetylating transcription factors and co-factors, SIRT1modulatesmetabolism, inflamma- tion, hypoxic responses, circadian rhythms, cell survival, and longevity. Since SIRT1 plays a key role in regulating pathways involved in cardiovascular diseases and metabolic diseases cancer, the regulation of SIRT1 has received intense scrutiny.The post-transcriptional regu- lation of SIRT1 is mediated by two classes of molecules, RNA-binding proteins (RBPs) and non-coding small RNAs. MicroRNAs (miRNAs) are short non-coding RNAs that regulate target gene expression in a post-transcriptional manner. More than 16 miRNAs modulate SIRT1 expression, including miR-34a. miR-34a induces colon cancer apoptosis through SIRT1, and miR-34a also promotes senescence in endothelial cells via SIRT1. This review describes the impact of miRNAs on SIRT1. The background of SIRT1 and miRNAs will be summarized, followed by the mechanism by which several key miRNAs alter SIRT1 levels, and how the RBP HuR regulates SIRT1. MicroRNA regulation of SIRT1 might affect a wide variety of pathways in humans, frommetabolic diseases such as diabetes to cardiovascular diseases and cancer. Keywords: microRNA, SIRT1, miR-34a, RNA-binding proteins, HuR SIRT1 O