The H2BG53D oncohistone directly upregulates ANXA3 transcription and enhances cell migration in pancreatic ductal adenocarcinoma

Wan, Yi Ching Esther; Liu, Jiaxian; Zhu, Lina; Kang, Tze Zhen Evangeline; Zhu, Xiaoxuan; Lis, John T.; Ishibashi, Toyotaka; Danko, Charles G.; Wang, Xin; Chan, Kui Ming

doi:10.1038/s41392-020-00219-2

Cited by 13 publications

(5 citation statements)

References 5 publications

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“…Then, GO and REACTOME pathway analyses were used to investigate the interactions of these DEGs. Lysosomal protein transmembrane 4 beta ( LAPTM4B ), 52 CEA cell adhesion molecule 6 ( CEACAM6 ), 53 serpin family E member 2 ( SERPINE2 ), 54 vanin 1 ( VNN1 ), 55 sphingosine kinase 1 ( SPHK1 ), 56 histidine rich glycoprotein ( HRG ), 57 vascular endothelial growth factor C ( VEGFC ), 58 annexin A3 ( ANXA3 ), 59 apolipoprotein A2 ( APOA2 ), 60 lipocalin 2 ( LCN2 ), 61 TIMP metallopeptidase inhibitor 1 ( TIMP1 ), 62 CD63 molecule ( CD63 ), 63 CD151 molecule (Raph blood group) ( CD151 ), 64 mal, T-cell differentiation protein 2 ( MAL2 ), 65 aryl hydrocarbon receptor nuclear translocator-like 2 ( ARNTL2 ), 66 polycystin 2, transient receptor potential cation channel ( PKD2 ), 67 E2F transcription factor 1 ( E2F1 ), 68 matrix metallopeptidase 1 ( MMP1 ), 69 C-C motif chemokine receptor 7 ( CCR7 ), 70 notch receptor 2 ( NOTCH2 ), 71 B and T lymphocyte associated ( BTLA ), 72 transferrin receptor ( TFRC ), 73 CD4 molecule ( CD4 ), 74 ATM serine/threonine kinase ( ATM ), 75 lymphoid enhancer binding factor 1 ( LEF1 ), 76 colony stimulating factor 1 receptor ( CSF1R ), 77 cathepsin B ( CTSB ), 78 dual specificity phosphatase 2 ( DUSP2 ), 79 and nuclear receptor subfamily 4 group A member 1 ( NR4A1 ) 80 are pathogenic genes for PDAC. Prostaglandin E receptor 3 ( PTGER3 ) 81 and membrane associated guanylate kinase, WW and PDZ domain containing 2 ( MAGI2 ) 82 have been reported to encourage the development of angiogenesis, chemoresistance, cell proliferation, and migration in ovary cancer.…”

Section: Discussionmentioning

confidence: 99%

Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Bioinformatics and Next-Generation Sequencing Data Analysis

Giriyappagoudar,

Vastrad,

Horakeri

et al. 2023

Bioinform Biol Insights

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Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common cancers worldwide. Intense efforts have been made to elucidate the molecular pathogenesis, but the molecular mechanisms of PDAC are still not well understood. The purpose of this study is to further explore the molecular mechanism of PDAC through integrated bioinformatics analysis. Methods: To identify the candidate genes in the carcinogenesis and progression of PDAC, next-generation sequencing (NGS) data set GSE133684 was downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and Gene Ontology (GO) and pathway enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using Integrated Interactions Database (IID) interactome database and Cytoscape. Subsequently, miRNA-DEG regulatory network and TF-DEG regulatory network were constructed using miRNet database, NetworkAnalyst database, and Cytoscape software. The expression levels of hub genes were validated based on Kaplan-Meier analysis, expression analysis, stage analysis, mutation analysis, protein expression analysis, immune infiltration analysis, and receiver operating characteristic (ROC) curve analysis. Results: A total of 463 DEGs were identified, consisting of 232 upregulated genes and 233 downregulated genes. The enriched GO terms and pathways of the DEGs include vesicle organization, secretory vesicle, protein dimerization activity, lymphocyte activation, cell surface, transferase activity, transferring phosphorus-containing groups, hemostasis, and adaptive immune system. Four hub genes (namely, cathepsin B [CCNB1], four-and-a-half LIM domains 2 (FHL2), major histocompatibility complex, class II, DP alpha 1 (HLA-DPA1) and tubulin beta 1 class VI (TUBB1)) were obtained via taking interaction of different analysis results. Conclusions: On the whole, the findings of this investigation enhance our understanding of the potential molecular mechanisms of PDAC and provide potential targets for further investigation.

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Section: Discussionmentioning

confidence: 99%

Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Bioinformatics and Next-Generation Sequencing Data Analysis

Giriyappagoudar,

Vastrad,

Horakeri

et al. 2023

Bioinform Biol Insights

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“…Mutation in histone proteins can also have an oncogenic effect [ 84 ]. One of the mutations, H2BG53D (termed oncohistone), is associated with the progression of pancreatic cancer [ 85 , 86 ]. However, the effect of oncohistone mutation on pancreatic cancer progression is not well elucidated.…”

Section: Histone Methylationmentioning

confidence: 99%

Epigenetic regulation of pancreatic adenocarcinoma in the era of cancer immunotherapy

2022

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Pancreatic adenocarcinoma is a lethal cancer with poor response to chemotherapy and immune checkpoint inhibitors. Recent studies suggest that epigenetic alterations contribute to its aggressive biology and the tumor microenvironment which render it unresponsive to immune checkpoint blockade. Here, we review our current understandings of epigenetic dysregulation in pancreatic adenocarcinoma, its effect on the tumor immune microenvironment, and the potential for epigenetic therapy to be combined with immune checkpoint inhibitors.

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“…For instance, Wang et al found that ANLN-induced EZH2 upregulation mediated the miR-218-5p/LASP1 signaling axis to promote PC progression 26 . Annexin A3 (ANXA3) expression levels were higher in PC patients carrying the H2BG53D mutation and were associated with worse patient outcomes 28 . NT5E (5'-Nucleotidase Ecto, CD73) is a transmembrane glycoprotein that promotes the initiation, metastasis, chemotherapy resistance, angiogenesis, and immune evasion of various cancers 29 – 34 .…”

Section: Discussionmentioning

confidence: 99%

Integrated single-cell and bulk RNA sequencing in pancreatic cancer identifies disulfidptosis-associated molecular subtypes and prognostic signature

Wu,

Shang,

Ruan

et al. 2023

Sci Rep

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Pancreatic cancer (PC) is known for its high degree of heterogeneity and exceptionally adverse outcome. While disulfidptosis is the most recently identified form of cell death, the predictive and therapeutic value of disulfidptosis-related genes (DRGs) for PC remains unknown. RNA sequencing data with the follow-up information, were retrieved from the TCGA and ICGC databases. Consensus clustering analysis was conducted on patient data using R software. Subsequently, the LASSO regression analysis was conducted to create a prognostic signature for foreseeing the outcome of PC. Differences in relevant pathways, mutational landscape, and tumor immune microenvironment were compared between PC samples with different risk levels. Finally, we experimentally confirmed the impact of DSG3 on the invasion and migration abilities of PC cells. All twenty DRGs were found to be hyperexpressed in PC tissues, and fourteen of them significantly associated with PC survival. Using consensus clustering analysis based on these DRGs, four DRclusters were identified. Additionally, altogether 223 differential genes were evaluated between clusters, indicating potential biological differences between them. Four gene clusters (geneClusters) were recognized according to these genes, and a 10-gene prognostic signature was created. High-risk patients were found to be primarily enriched in signaling pathways related to the cell cycle and p53. Furthermore, the rate of mutations was markedly higher in high-risk patients, besides important variations were present in terms of immune microenvironment and chemotherapy sensitivity among patients with different risk levels. DSG3 could appreciably enhance the invasion and migration of PC cells. This work, based on disulfidoptosis-related genes (DRGs), holds the promise of classifying PC patients and predicting their prognosis, mutational landscape, immune microenvironment, and drug therapy. These insights could boost an improvement in a better comprehension of the role of DRGs in PC as well as provide new opportunities for prognostic prediction and more effective treatment strategies.

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The H2BG53D oncohistone directly upregulates ANXA3 transcription and enhances cell migration in pancreatic ductal adenocarcinoma

Cited by 13 publications

References 5 publications

Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Bioinformatics and Next-Generation Sequencing Data Analysis

Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Bioinformatics and Next-Generation Sequencing Data Analysis

Epigenetic regulation of pancreatic adenocarcinoma in the era of cancer immunotherapy

Integrated single-cell and bulk RNA sequencing in pancreatic cancer identifies disulfidptosis-associated molecular subtypes and prognostic signature

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