Genome-wide RNA-seq from control vector- and GALNT3-overexpressed H2030 cell lines
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE156045 | GEO | 2023/08/11
REPOSITORIES: GEO
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Project description:Genome-wide RNA-seq from control vector- and GALNT3-overexpressed H2030 cell lines
| PRJNA656536 | ENA
Project description:Despite the dual roles of GALNT3 in various cellular processes related to tumorigenesis and solid tumors, the clinical and biological significance of GALNT3 in lymphomagenesis remains largely unknown. Herein, our bioinformatics analysis uncovers that GALNT3 dependent glucose metabolism was significantly elevated in DLBCL. Our DLBCL cohort study revealed that GALNT3 positivity is significantly associated with worse prognosis and clinical outcomes in DLBCL pathogenesis. Biologically, GALNT3 overexpression were found to promote DLBCL cell proliferation and cell cycle progression, while silencing GALNT3 inhibited lymphomagenesis. RNA-seq uncovers that GALNT3 upregulated FGFR2-MAPK signaling pathway in DLBCL. Moreover, protein mass spectrometry identified two potential O-glycosylation sites of FGFR2 (Thr319 and Ser299). Further point mutation of glycosylation sites, confirmed that GALNT3 O-glycosylates FGFR2 through Thr319. Besides, in vitro and in vivo rescue experiments demonstrated that Thr319 is dispensable for GALNT3-FGFR2-MAPK induced lymphomagenesis. In vitro pharmacological inhibition of FGFR2 with a selective inhibitor Futibatinib further demonstrated that Futibatinib inhibits DLBCL cell growth, cell proliferation, induced cell cycle arrest, promoted cell apoptosis. Further in vivo study also indicated that combination of Futibatinib with chemotherapy demonstrated better anti-tumor activity relative to single drug therapy in DLBCL treatment. Collectively, our data highlight the importance of considering the GALNT3-FGFR2-MAPK signaling axis as an attractive therapeutic target for lymphomagenesis.
2026-01-28 | GSE285695 | GEO
Project description:Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, thus understanding molecular changes associated with EOC progression could lead to the identification of essential therapeutic targets. Glycosylation is a post-translational modification (PTM) that participates in major pathophysiology events, including tumorigenesis. Aberrant mucin-type or O-glycosylation in cancer is frequently attributed to altered expression of different N-acetylgalactosaminyltransferases (GalNAc-Ts). We have previously identified the N-acetylgalactosaminyltransferase 3 (GALNT3) gene as a potential EOC oncogene, possibly implicated in aberrant O-glycosylation in EOC cells. Literature reports are suggestive for genetic and functional redundancy between different GalNAc-Ts, and our previous data were indicative for an induction of the GALNT6 expression upon GALNT3 suppression in EOC cells. Here we show that GALNT3 gene knockout (KO) in the A2780s EOC cells leads to strong GALNT6 upregulation. Moreover, A2780s cell migration, invasion, proliferation and cell cycle analysis were significantly reduced in double GALNT3/T6 gene KO cells compared to single GALNT3 gene KO. Furthermore, MUC1 expression was downregulated in both GALNT3 KO and GALNT3/6 KO, with a more prominent decrease observed in the double KO clone. In vivo studies supported the observed functional redundancy imposed by GALNT6, as animals injected with double GALNT3/T6 KO EOC cell clones displayed a significant increase in survival rates compared to those injected with the control and the GALNT3 KO clones. Collectively our data strongly suggest for possible functional redundancy of the two GalNAc-Ts (GALNT3 and T6) in EOC, with the perspective to use both of these genes as EOC markers and/or therapeutic targets.
2019-05-07 | GSE104861 | GEO
Project description:The UDP-N-acetylgalactosamine polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes initiates O-linked glycosylation by catalyzing the addition of the first GalNAc sugar to serine or threonine on proteins destined to be membrane-bound or secreted. Defects in individual isoforms of the GalNAc-T family can lead to certain congenital disorders of glycosylation (CDG). The GALNT3-CDG, is caused by mutations in GALNT3, resulting in hyperphosphatemic familial tumoral calcinosis (HFTC) due to impaired glycosylation of the phosphate-regulating hormone FGF23 within osteocytes of the bone. Patients with hyperphosphatemia present altered bone density, abnormal tooth structure and calcified masses throughout the body. It is therefore important to identify all potential substrates of GalNAc-T3 throughout the body to understand the complex disease phenotypes. Here, we compared the Galnt3-/- mouse model, which partially phenocopies GALNT3-CDG, with wild-type mice and employed a multi-component approach utilizing chemoenzymatic conditions, a product-dependent method constructed using EThcD triggered scans in a mass spectrometry workflow, quantitative O-glycoproteomics, and global proteomics to identify 663 Galnt3-specific O-glycosites from 269 glycoproteins across multiple tissues. Consistent with the mouse and human phenotypes, functional networks of glycoproteins that contain GalNAc-T3-specific O-glycosites involved in skeletal morphology, mineral level maintenance and hemostasis were identified. This library of in vivo GalNAc-T3-specific substrate proteins and O-glycosites will serve as a valuable resource to understand the functional implications of O-glycosylation and to unravel the underlying causes of complex human GALNT3-CDG phenotypes.
2025-05-07 | PXD053014 | Pride
Project description:The UDP-N-acetylgalactosamine polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes initiates O-linked glycosylation by catalyzing the addition of the first GalNAc sugar to serine or threonine on proteins destined to be membrane-bound or secreted. Defects in individual isoforms of the GalNAc-T family can lead to certain congenital disorders of glycosylation (CDG). The GALNT3-CDG, is caused by mutations in GALNT3, resulting in hyperphosphatemic familial tumoral calcinosis (HFTC) due to impaired glycosylation of the phosphate-regulating hormone FGF23 within osteocytes of the bone. Patients with hyperphosphatemia present altered bone density, abnormal tooth structure and calcified masses throughout the body. It is therefore important to identify all potential substrates of GalNAc-T3 throughout the body to understand the complex disease phenotypes. Here, we compared the Galnt3-/- mouse model, which partially phenocopies GALNT3-CDG, with wild-type mice and employed a multi-component approach utilizing chemoenzymatic conditions, a product-dependent method constructed using EThcD triggered scans in a mass spectrometry workflow, quantitative O-glycoproteomics, and global proteomics to identify 663 Galnt3-specific O-glycosites from 269 glycoproteins across multiple tissues. Consistent with the mouse and human phenotypes, functional networks of glycoproteins that contain GalNAc-T3-specific O-glycosites involved in skeletal morphology, mineral level maintenance and hemostasis were identified. This library of in vivo GalNAc-T3-specific substrate proteins and O-glycosites will serve as a valuable resource to understand the functional implications of O-glycosylation and to unravel the underlying causes of complex human GALNT3-CDG phenotypes.
2025-05-07 | PXD052978 | Pride
Project description:The polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes initiates O-linked glycosylation by catalyzing the addition of the first GalNAc sugar to serine or threonine on proteins destined to be membrane-bound or secreted. Defects in individual isoforms of the GalNAc-T family can lead to congenital disorders of glycosylation (CDG). The GALNT3-CDG, is caused by mutations in GALNT3, resulting in hyperphosphatemic familial tumoral calcinosis (HFTC) due to impaired glycosylation of the phosphate-regulating hormone FGF23 within osteocytes of the bone. Patients with hyperphosphatemia present altered bone density, abnormal tooth structure and calcified masses throughout the body. It is therefore important to identify all potential substrates of GalNAc-T3 throughout the body to understand the complex disease phenotypes. Here, we compared the Galnt3-/- mouse model, which partially phenocopies GALNT3-CDG, with wild-type and employed a multi-component approach utilizing chemoenzymatic conditions, a product-dependent method constructed using EThcD triggered scans in mass spectrometry workflow, quantitative O-glycoproteomics and global proteomics to identify 663 Galnt3-specific O-glycosites from 269 glycoproteins across multiple tissues. Consistent with the mouse and human phenotypes, functional networks of glycoproteins that contain GalNAc-T3-specific O-glycosites that are involved in skeletal morphology, mineral level maintenance and hemostasis. The generated library of in vivo GalNAc-T3-specific substrate proteins and O-glycosites serves as a valuable resource to understand the functional implications of O-glycosylation and to unravel the underlying causes of complex human CDG phenotypes.
2025-05-06 | PXD047517 | Pride
Project description:Gene expression changes were compared in proliferating and senescent human IMR90 cells, with either empty vector, Parkin, or Parkin+CCCP. Method: RNA was extracted, in triplicate, then sequenced with an Illumina NextSeq 500 sequencer. Sequence reads passing the quality control filters were aligned using Tophat2 and then analysed with Cufflinks.
2020-06-30 | GSE132369 | GEO
Project description:An equal mixture of cells from the 3 Human Lung Adenocarcinoma cell lines (H2228, NCI-H1975 and HCC827) were processed on the Chromium 3' single cell platform (10X Genomics) and sequenced on an Illumina NextSeq 500. FASTQ data were preprocessed using both scPipe and CellRanger.
2018-02-28 | GSE111108 | GEO
Project description:Viral infections affecting the upper or lower respiratory tract induce mucin production in the epithelial surfaces of the respiratory cells. However, a little is known about how mucins are produced on the surfaces of respiratory epithelial cells and affects viral replication. In the course of the investigation of the cellular responses in the early stage of Influenza A virus (IAV) infection, we found that two miRNAs, miR-221 and miR-17-3p, which target the mRNA of GalNAc transferase 3 (GALNT3), are rapidly down-regulated as early as 1.5 h post-infection.
2015-12-08 | GSE57508 | GEO