PHGDH acts as an RNA-binding protein to stabilize PRKCD mRNA and promote hepatocellular carcinoma progression
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE268485 | GEO | 2025/06/12
REPOSITORIES: GEO
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Project description:PHGDH acts as an RNA-binding protein to stabilize PRKCD mRNA and promote hepatocellular carcinoma progression
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Project description:Transcriptional profiling of human hepatoellular carcinoma (HCC) cell line: MHCC-97H comparing control untreated MHCC-97H cells with MHCC-97H cells overexpressed ROCK1 protein. Goal was to determine the effect of ROCK1 on global MHCC-97H cell mRNA and lncRNA expression. Transcriptional profiling of human hepatoellular carcinoma (HCC) cell line: MHCC-97H comparing control untreated MHCC-97H cells with MHCC-97H cells overexpressed ROCK2 protein. Goal was to determine the effect of ROCK2 on global MHCC-97H cell mRNA and lncRNA expression. Transcriptional profiling of human hepatoellular carcinoma (HCC) cell line: MHCC-97H comparing MHCC-97H cells overexpressed ROCK1 with MHCC-97H cells overexpressed ROCK2 protein. Goal was to determine the distinction of ROCK1 & 2 on global MHCC-97H cell mRNA and lncRNA expression.
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Project description:PHGDH acts as an RNA-binding protein to stabilize PRKCD mRNA and promote hepatocellular carcinoma progression
| PRJNA1117445 | ENA
Project description:TGM2 IP-MS was performed in MHCC-97H cells to screen the interactors of TGM2. 5-PT pulldown-MS was perfromed in MHCC-97H cells to identify proteins modified by serotonylation.
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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.
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Project description:Hepatocellular carcinoma (HCC) ranks among one of the most prevalent and lethal cancers affecting humans. Currently, there are limited effective treatments available for HCC. In the search for potential anti-HCC agents, we found that carfilzomib, a proteasome inhibitor, exerts anti-HCC activities. However, the underlying mechanisms of action are main unclear. In this study, we evaluated the effectiveness of carfilzomib against HCC capability and explored its underlying mechanisms. Cell Counting Kit 8 (CCK8), EdU (5-ethynyl-2-deoxyuridine) staining, and colony formation assays were employed to analyze the antiproliferative ability of carfilzomib on MHCC-97H and Huh7 cells. Additionally, flow cytometry was used to assess the effect on the cell cycle. Western blotting was utilized to examine the protein expression levels associated with cell cycle arrest. Furthermore, short hairpin RNA (shRNA) transfection was used to investigate the role of GADD45a (growth arrest and DNA damage 45a) on carfilzomib-induced cell cycle arrest. A xenograft tumor model using nude mouse was employed to evaluate the anti-HCC activity of carfilzomib in vivo. The finding demonstrated that carfilzomib inhibited the proliferation, invasion, and migration in both MHCC-97H and Huh7 cells. In addition, carfilzomib caused cell cycle arrest by suppressing the expression of cyclin A1, cyclin E1, cyclin-dependent kinases 2 (CDK2), and cyclin-dependent kinases 4 (CDK4). It also upregulated the expression of GADD45a, and inhibition of GADD45a through shRNA abolished carfilzomib-induced cell cycle arrest in HCC cells. Importantly, carfilzomib demonstrated its ability to inhibit the Huh7 cell growth in vivo. Our research has revealed, for the first time, that carfilzomib inhibited the progression of HCC cells by upregulating GADD45a expression. These findings suggest that carfilzomib could be a potential chemotherapeutic agent against HCC.
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2019-02-12 | GSE97387 | GEO
Project description: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 HCC tissues is increased, whereas the expression of phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in serine biosynthesis pathway, is dramatically downregulated. Interestingly, the increased serine level is obtained by enhanced PHGDH catalytic activity due to protein arginine methyltransferase 1 (PRMT1)-mediated methylation of PHGDH at arginine 236. PRMT1-mediated PHGDH methylation and activation potentiates serine synthesis, ameliorates oxidative stress, and promotes HCC growth in vitro and in vivo. FBXO7, an E3 ubiquitin ligase which is downregulated in human HCC tissues, ubiquitinates and downregulates PRMT1 to suppress PHGDH methylation and serine synthesis, leading to the inhibition of HCC cell growth. Furthermore, PRMT1-mediated PHGDH methylation correlates with PHGDH hyperactivation and serine accumulation in human HCC tissues, and is predictive of poor prognosis of HCC patients. Notably, blocking PHGDH methylation with a TAT-tagged non-methylated peptide inhibits serine synthesis and restrains HCC growth, both in an HCC patient-derived xenograft (PDX) model and subcutaneous HCC cell-derived xenograft model. Overall, our findings reveal a novel regulatory mechanism of PHGDH activity and serine synthesis, and suggest PHGDH methylation as a potential therapeutic vulnerability in HCC.
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Project description:Tumor-associated macrophages (TAMs) are crucial components of the tumor microenvironment (TME). They play vital roles in hepatocellular carcinoma (HCC) progression. However, the interactions between TAMs and HCC cells have not been fully characterized. In this study, TAMs were induced using human monocytic cell line THP-1 cells in vitro to investigate their functions in HCC progression. S100 calcium binding protein A9 (S100A9), an inflammatory microenvironment-related secreted protein, was identified to be significantly upregulated in TAMs. S100A9 expression in tumor tissues was associated with poor survival of HCC patients. It could enhance the stem cell-like properties of HepG2 and MHCC-97H cells by activating nuclear factor-kappa B (NF-κB) signaling pathway through advanced glycosylation end-product specific receptor (AGER) in a Ca2+-dependent manner. Furthermore, we found that, after treatment with S100A9, HepG2 and MHCC-97H cells recruited more macrophages via chemokine (C-C Motif) ligand 2 (CCL2), which suggests a positive feedback between TAMs and HCC cells. Taken together, our findings reveal that TAMs could upregulate secreted protein S100A9 and enhance the stem cell-like properties of HCC cells, and provide a potential therapeutic target for combating HCC.
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Project description:To study the mRNA modulating network and different expressed mRNA lists in MHCC-97H-SH-UCK2 cells, we use high-throughout method to genomically detect the expression profile of mRNA
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