A systematic study of the cellular metabolic regulation of Jhdm1b in tumor cells

Abstract

Metabolic alterations have been observed in cancer for almost a century. Much attention is now directed toward the mechanisms underlying these changes. Jhdm1b (Fbxl10/Kdm2b), an H3K4/K36 histone demethylase overexpressed in various types of cancer, has been reported to regulate cell proliferation and senescence in HeLa cells. In this work, we used ¹³C stable isotope resolved metabolomics to investigate cellular metabolites, including intermediates of glycolysis, the pentose phosphate pathway, and the Krebs cycle. The difference in the concentration of cellular metabolites of wild-type and Jhdm1b knockdown HeLa cells indicates that Jhdm1b is a positive regulator of glycolysis, glutaminolysis, and pyrimidine synthesis in HeLa cells. Double knockdown experiments showed that receptor-interacting serine/threonine-protein kinase 3(RIP3), a protein kinase of the cell, is critical to the metabolic shifts induced by Jhdm1b depletion.