TY - JOUR AB - In response to various cellular stresses, p53 exerts its tumor suppressive effects such as apoptosis, cell cycle arrest, and senescence through the induction of its target genes. Recently, p53 was shown to control cellular homeostasis by regulating energy metabolism, glycolysis, antioxidant effect, and autophagy. However, its function in inositol synthesis was not reported. Through a microarray screening, we found that five genes related with myo-inositol metabolism were induced by p53. DNA damage enhanced intracellular myo-inositol content in HCT116 p53+/+ cells, but not in HCT116 p53-/- cells. We also indicated that inositol 3-phosphate synthase (ISYNA1) which encodes an enzyme essential for myo-inositol biosynthesis as a direct target of p53. Activated p53 regulated ISYNA1 expression through p53 response element in the seventh exon. Ectopic ISYNA1 expression increased myo-inositol levels in the cells and suppressed tumor cell growth. Knockdown of ISYNA1 caused resistance to adriamycin treatment, demonstrating the role of ISYNA1 in p53-mediated growth suppression. Furthermore, ISYNA1 expression was significantly associated with p53 mutation in bladder, breast cancer, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and pancreatic adenocarcinoma. Our findings revealed a novel role of p53 in myo-inositol biosynthesis which could be a potential therapeutic target. AD - Laboratory of Clinical Sequence, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan AU - Koguchi,Tomoyuki AU - Tanikawa,Chizu AU - Mori,Jinichi AU - Kojima,Yoshiyuki AU - Matsuda,Koichi DA - 2016/06/01 DO - 10.3892/ijo.2016.3456 EP - 2424 IS - 6 JO - Int J Oncol KW - p53 inositol 3-phosphate synthase myo-inositol PY - 2016 SN - 1019-6439 1791-2423 SP - 2415 ST - Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway T2 - International Journal of Oncology TI - Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway UR - https://doi.org/10.3892/ijo.2016.3456 VL - 48 ER -