Dataset Information

PHGDH Arginine Methylation by PRMT1 Promotes Serine Synthesis and Represents a Therapeutic Vulnerability in Hepatocellular Carcinoma

ABSTRACT: Serine synthesis is crucial for tumor growth and survival, but its regulatory mechanism in cancer remains elusive. Here, we found that R236 methylation of PHGDH promotes its activity and stimulates serine synthesis in hepatocellular carcinoma.

ORGANISM(S): Homo Sapiens

SUBMITTER: Canhua Huang

PROVIDER: PXD035061 | iProX | Thu Jul 28 00:00:00 BST 2022

REPOSITORIES: iProX

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Publications

PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma.

Wang Kui K Luo Li L Fu Shuyue S Wang Mao M Wang Zihao Z Dong Lixia L Wu Xingyun X Dai Lunzhi L Peng Yong Y Shen Guobo G Chen Hai-Ning HN Nice Edouard Collins EC Wei Xiawei X Huang Canhua C

Nature communications 20230223 1

Serine synthesis is crucial for tumor growth and survival, but its regulatory mechanism in cancer remains elusive. Here, using integrative metabolomics and transcriptomics analyses, we show a heterogeneity between metabolite and transcript profiles. Specifically, the level of serine in hepatocellular carcinoma (HCC) tissues is increased, whereas the expression of phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in serine biosynthesis pathway, is markedly downregulated. Inte ...[more]

PMID: 36823188

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Project description:D-3-Phosphoglycerate dehydrogenase (Phgdh; EC 1.1.1.95) is a necessary enzyme for de novo L-serine biosynthesis via the phosphorylated pathway. We demonstrated previously that Phgdh is expressed exclusively by neuroepithelium and radial glia in developing mouse brain and later mainly by astrocytes. Mutations in the human PHGDH gene cause serine deficiency disorders (SDD) associated with severe neurological symptoms such as congenital microcephaly, psychomotor retardation, and intractable seizures. We recently demonstrated that genetically engineered mice, in which the gene for Phgdh has been disrupted, have significantly decreased levels of serine and glycine, and exhibit malformation of brain such as microcephaly. The Phgdh null (KO) embryos exhibit lethal phenotype after gestational day 14, indicating that the phosphorylated pathway is essential for embryogenesis, especially for brain development. It is worth noting that the Phgdh knockout (KO) embryos primarily displayed microcephaly, which is the most conspicuous phenotype of patients with SDD. Thus, Phgdh KO mice are a useful animal model for studying the effect of diminished L-serine levels on development of the central nervous system and other organs. To better understand the mechanism underlying the molecular pathogenesis of SDD, we sought to examine whether gene expression is altered in the Phgdh KO mouse model. We identify genes that have altered expression in the head of the Phgdh KO embryos using the GeneChip array. Some of the genes identified by this method belong in functional categories that are relevant to the biochemical and morphological aberrations of the Phgdh deletion. Experiment Overall Design: Total RNA samples were prepared from head tissues from 2 embryos of Phgdh knockout and littermate wild-type controls. Experiment Overall Design: RNA of 4 biological replicates was hybridized to Affymetrix Mouse Genome 430 2.0 arrays. Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.

Dataset Information

PHGDH Arginine Methylation by PRMT1 Promotes Serine Synthesis and Represents a Therapeutic Vulnerability in Hepatocellular Carcinoma

Publications

PHGDH arginine methylation by PRMT1 promotes serine synthesis and represents a therapeutic vulnerability in hepatocellular carcinoma.

Similar Datasets

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