An NAD<sup>+</sup> dependent/sensitive transcription system: Toward a novel anti-cancer therapy

Abstract

Cancer is widely known as a “genetic disease” because almost all cancers involve genomic mutations. However, cancer could also be referred to as a metabolic disease because it mainly depends on glycolysis to produce adenosine triphosphate (ATP) and is frequently accompanied by dysfunctions in the mitochondria, which are the primary organelle required in all eukaryotic cells. Importantly, almost all (99%) mitochondrial proteins are encoded by host nuclear genes. Not only cancer but also aging-related diseases, including neurodegenerative diseases, are associated with a decline in mitochondrial functions. Importantly, the nicotinamide adenine dinucleotide (NAD+) level decreases with aging. This molecule not only plays important roles in metabolism but also in the DNA repair system. In this article, we review 5′-upstream regions of mitochondrial function-associated genes to discuss the possibility of whether NAD+ is involved in transcriptional regulations. If the expression of these genes declines with aging, this may cause mitochondrial dysfunction. In this regard, cancer could be referred to as a “transcriptional disease”, and if so, novel therapeutics for cancer will need to be developed.