GSE161730
An integrated RNA-Seq and network study reveals the effect of nicotinamide on adrenal androgen synthesis
Acne vulgaris is a chronic inflammatory disease of the skin resulting from androgeninduced  increased sebum production and altered keratinization. Nicotinamide (NAM),  an amide form of vitamin B3 with a well-established safety profile, has shown good  therapeutic potential in treating acne and its complications. NAM has anti-inflammatory  effects and reduces sebum but its function in androgen biosynthesis remains  unknown. In this study, we used a widely used cell model, starved human adrenal  NCI-H295R cells, to examine the effects of NAM in androgen production and its mediated  network changes. By treating NCI-H295R cells with 1-25 mmol/L of NAM, we  found that cell viability was only slightly inhibited at the highest dose (25 mmol/L).  NAM reduced testosterone production in a dose-dependent manner. Transcriptomic  analysis demonstrated that key enzymes of androgen biosynthesis were significantly  decreased under NAM treatment. In addition, gene set enrichment analysis (GSEA)  showed that gene sets of cell cycle, steroid biosynthesis, TGFß signalling, and targets  of IGF1 or IGF2 were enriched in NAM-treated cells. Kyoto Encyclopaedia of Genes  and Genomes (KEGG) pathway and Gene ontology (GO) analysis of the differentially  expressed genes also suggested that steroidogenesis and SMAD signalling were affected  by NAM. Overall, these crucial genes and pathways might form a complex  network in NAM-treated NCI-H295R cells and result in androgen reduction. These  findings help explain the potential molecular actions of NAM in acne vulgaris, and  position NAM as a candidate for the treatment of other hyperandrogenic disorders. Overall design: starved NCI-H295R cells treated  with or without 25 mmol/L NAM for 24 hours