Interplay Among Metabolism, Epigenetic Modifications, and Gene Expression in Cancer

Epigenetic modifications and metabolism are two fundamental biological processes. During tumorigenesis and cancer development both epigenetic and metabolic alterations occur and are often intertwined together. Epigenetic modifications contribute to metabolic reprogramming by modifying the transcriptional regulation of metabolic enzymes, which is crucial for glucose metabolism, lipid metabolism, and amino acid metabolism. Metabolites provide substrates for epigenetic modifications, including histone modification (methylation, acetylation, and phosphorylation), DNA and RNA methylation and non-coding RNAs. Simultaneously, some metabolites can also serve as substrates for nonhistone post-translational modifications that have an impact on the development of tumors. And metabolic enzymes also regulate epigenetic modifications independent of their metabolites. In addition, metabolites produced by gut microbiota influence host metabolism. Understanding the crosstalk among metabolism, epigenetic modifications, and gene expression in cancer may help researchers explore the mechanisms of carcinogenesis and progression to metastasis, thereby provide strategies for the prevention and therapy of cancer. In this review, we summarize the progress in the understanding of the interactions between cancer metabolism and epigenetics.

Impact of Glyphosate Exposure on Glycogen Metabolic Enzymes in the Liver of Adult Male Rats

Background: Glyphosate is a broad spectrum herbicide and desiccant. Diabetes is a group of metabolic diseases resulting due to deficiency in insulin secretion. Chronic hyperglycemia will lead to long term damage and failure of different organs like eyes, kidneys, nerves etc. Liver is the major site for gluconeogenesis and a lot of glycolytic enzymes will be involved. Expression of Glycogen synthase and glycogen phosphorylase, the glycolytic enzymes are studied in this research. Aim: To determine whether glyphosate exposure is detrimental to the glycogen metabolic enzymes (Glycogen synthase and phosphorylase) in the liver of adult male rats. Materials and Methods: The following study was done on albino rats of wistar strain, and was approved by the institutional animal ethics committee. They were fed with a rat pellet diet. In our study the rats were divided into 4 groups with 6 rats in each and were subjected to glyphosate orally with different dosage in each group and mRNA expression analysis of glycogen related enzymes was done after a span of 16 weeks. The data were analyzed statistically by a one way analysis of variance (ANOVA) followed by Duncan’s multiple range test was used to see the statistical significance among the group. The results with p<0.05 level were considered to be statistically significant. Results: The present result showed that the mRNA expression of glycogen synthase significantly reduced (P<0.05) and mRNA expression of glycogen phosphorylase activity increased significantly with an increased dose of glyphosate (P<0.05) to that of control. Conclusion: Exposure to glyphosate causes detrimental changes in the glycolytic enzymes glycogen synthase and glycogen phosphorylase leading to diabetes.

Thomas Arthur Steitz. 23 August 1940—9 October 2018

Thomas A. Steitz was among the foremost of the generation that was responsible for an explosion in our understanding of the structure and function of biological macromolecules. His research career was one of sustained excellence over six decades, and spanned the range from determining the structures of important metabolic enzymes to understanding the structural basis of how genetic information residing in our DNA is used to make the proteins they encode. This latter effort culminated in the structure of the ribosome, for which he shared the Nobel Prize in Chemistry in 2009.