Extensive regulation of nicotinate phosphoribosyltransferase (NAPRT) expression in human tissues and tumors

烟酸磷酸核糖基转移酶 (NAPRT) 在人体组织和肿瘤中的表达受到广泛调控

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作者:Sara Duarte-Pereira, Isabel Pereira-Castro, Sarah S Silva, Mariana Gonçalves Correia, Célia Neto, Luís Teixeira da Costa, António Amorim, Raquel M Silva

Abstract

Nicotinamide adenine dinucleotide (NAD) is a cofactor in redox reactions and a substrate for NAD-consuming enzymes, such as PARPs and sirtuins. As cancer cells have increased NAD requirements, the main NAD salvage enzymes in humans, nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate phosphoribosyltransferase (NAPRT), are involved in the development of novel anti-cancer therapies. Knowledge of the expression patterns of both genes in tissues and tumors is critical for the use of nicotinic acid (NA) as cytoprotective in therapies using NAMPT inhibitors. Herein, we provide a comprehensive study of NAPRT and NAMPT expression across human tissues and tumor cell lines. We show that both genes are widely expressed under normal conditions and describe the occurrence of novel NAPRT transcripts. Also, we explore some of the NAPRT gene expression mechanisms. Our findings underline that the efficiency of NA in treatments with NAMPT inhibitors is dependent on the knowledge of the expression profiles and regulation of both NAMPT and NAPRT.

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