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

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 (13)C 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.