Glutamine/Serine/Glycine concentration related KDM4A expression regulated cisplatin sensitivity in gastric cancer cells

Abstract

Abstract Gastric cancer is a high incidence of digestive system tumors, and the existence of drug resistance reduces the sensitivity to chemotherapy. Nutritional therapy can significantly improve the prognosis of tumor patients. Dietary amino acids play an important regulatory role in tumor gene expression, epigenetics, signal transduction, metabolic remodeling and other processes. This study found that glutamine, glycine and serine could significantly regulate the sensitivity of gastric cancer cells to cisplatin by screening 20 amino acids. When the concentration of glutamine, glycine and serine decreased, KDM4A underwent acetylation to maintain protein stability, activate DNA repair ability, and reduce the sensitivity of gastric cancer cells to chemotherapy. Conversely, when the concentration of glutamine, glycine and serine increased, ubiquitination degradation of KDM4A occurred, which improved the sensitivity of gastric cancer cells to chemotherapy. Our study systematically analyzed the role and mechanism of amino acid nutrition in regulating chemotherapy sensitivity of gastric cancer, thus providing scientific basis for expanding the value of tumor nutrition therapy.