Extensive regulation of nicotinate phosphoribosyltransferase (NAPRT) expression in human tissues and tumors
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Sara Duarte-Pereira1, Isabel Pereira-Castro1,6, Sarah S. Silva1, Mariana Gonçalves Correia1, Célia Neto1, Luís Teixeira da Costa1,2, António Amorim1,3,4 and Raquel M. Silva1,5
1 IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal
2 ICAAM - Instituto de Ciências Agrárias e Ambientais Mediterrânicas, University of Évora, Évora, Portugal
3 Faculty of Sciences, University of Porto, Porto, Portugal
4 Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal
5 Institute for Biomedicine - iBiMED & IEETA, University of Aveiro, Aveiro, Portugal
6 Gene Regulation Group, i3S/IBMC - Instituto de Investigação e Inovação em Saúde/Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
Raquel M. Silva, email:
Keywords: human NAD salvage, NAPRT, NAMPT, alternative transcripts, anti-cancer therapies
Received: June 23, 2015 Accepted: November 21, 2015 Published: December 09, 2015
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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