Concepts to Target MYC in Pancreatic Cancer

Wirth, Matthias; Mahboobi, Siavosh; Krämer, Oliver; Schneider, Günter

doi:10.1158/1535-7163.mct-16-0050

Cited by 66 publications

(67 citation statements)

References 84 publications

(101 reference statements)

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“…MYC acts as a carcinogenic transcription factor that regulates at least 15% of genes involved in various cellular processes, including the differentiation, cell proliferation, apoptosis, and metabolism of PC [56,57]. Additionally, the KRAS/ERK/c-Myc axis is the major driving factor of tumorigenesis in PC.…”

Section: Discussionmentioning

confidence: 99%

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Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

et al. 2019

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Pancreatic ductal adenocarcinoma (PDAC) is a class of the commonest malignant carcinomas. The present study aimed to elucidate the potential biomarker and prognostic targets in PDAC. The array data of GSE41368, GSE43795, GSE55643, and GSE41369 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) and differentially expressed microRNAs (DEmiRNAs) in PDAC were obtained by using GEO2R, and overlapped DEGs were acquired with Venn Diagrams. Functional enrichment analysis of overlapped DEGs and DEmiRNAs was conducted with Metascape and FunRich, respectively. The protein–protein interaction (PPI) network of overlapped DEGs was constructed by STRING and visualized with Cytoscape. Overall survival (OS) of DEmiRNAs and hub genes were investigated by Kaplan–Meier (KM) plotter (KM plotter). Transcriptional data and correlation analyses among hub genes were verified through GEPIA and Human Protein Atlas (HPA). Additionally, miRNA targets were searched using miRTarBase, then miRNA–DEG regulatory network was visualized with Cytoscape. A total of 32 DEmiRNAs and 150 overlapped DEGs were identified, and Metascape showed that DEGs were significantly enriched in cellular chemical homeostasis and pathways in cancer, while DEmiRNAs were mainly enriched in signal transduction and Glypican pathway. Moreover, seven hub genes with a high degree, namely, V-myc avian myelocytomatosis viral oncogene homolog (MYC), solute carrier family 2 member 1 (SLC2A1), PKM, plasminogen activator, urokinase (PLAU), peroxisome proliferator activated receptor γ (PPARG), MET proto-oncogene, receptor tyrosine kinase (MET), and integrin subunit α 3 (ITGA3), were identified and found to be up-regulated between PDAC and normal tissues. miR-135b, miR-221, miR-21, miR-27a, miR-199b-5p, miR-143, miR-196a, miR-655, miR-455-3p, miR-744 and hub genes predicted poor OS of PDAC. An integrative bioinformatics analysis identified several hub genes that may serve as potential biomarkers or targets for early diagnosis and precision target treatment of PDAC.

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Section: Discussionmentioning

confidence: 99%

“…In normal cells, MYC is a transient protein that is present from 20 to 30 min and is uncontrollable in cancers. Hence, promoting the degradation of MYC is a promising treatment strategy for PDAC [57]. Metabolic deregulation is a hallmark of human cancers.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

et al. 2019

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“…Studies also indicate a persistent maintenance role for Myc in established PDAC. myc knockdown inhibits proliferation of human PDAC cell lines in vitro 46 and direct 43 or indirect 47 inactivation of Myc triggers macroscopic regression of established PDAC in mouse models in vivo 48 , albeit with persistence of dormant tumor cells 43 . Taken together, these data suggest a critical role for Myc in both the progression from PanIN to PDAC and in subsequent PDAC maintenance 32 .…”

Section: Introductionmentioning

confidence: 99%

Myc instructs and maintains pancreatic adenocarcinoma phenotype

Sodir

Kortlever

Barthet

et al. 2019

Preprint

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KEYWORDSMyc, Ras, pancreatic cancer, microenvironment, desmoplasia, immune evasion. fibroinflammatory stroma is a product of complex interplay between tumor cells and adjacent mesenchymal, endothelial, inflammatory and immune cells and is thought to contribute to PDAC therapeutic recalcitrance by impeding vascular perfusion and oxygenation 10,11 .At the molecular level, PDAC is associated with a core of recurring, presumably causal, oncogenic mutations, of which activating mutations in KRas appear to be founder drivers and are present in over 90% of both PanINs and PDAC. Other frequently recurring signature mutations inactivate CDKN2A (90-95%), TP53 (50-84%) or SMAD4/DPC4 (49-55%) and recent, more granular, analyses reveal a plethora of additional sporadic PDAC mutations encompassing great functional diversity 5-7 . As the most commonly recurring oncogenic mutation, many of the canonical features of PDAC are attributed to precocious KRas signaling.

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“…In mature organs such as in the pancreas, MYC up-regulation is commonly associated with a cancer phenotype. For example, activation of MYC in mice has been shown to lead to the generation of pancreatic ductal adenocarcinoma [Hessmann et al, 2016;Wirth et al, 2016]. Rather, the aberrant expression of this gene by many upstream processes or by copy-number variations contributes to MYC dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Dissection of Transcriptome Data and Regulatory Factors in Pancreatic Cancer Cells

Akbari

Mohammadnia

Yaqubi

et al. 2017

J of Cellular Biochemistry

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Features of pancreatic cancers include high mortality rates caused by rapid tumor progression and a lack of effective therapy. Underpinning the molecular mechanisms involved in the alteration of the gene expression program in the pancreatic cancer remains to be understood. In the current study, we performed a comprehensive analysis using 282 pancreatic tumor and normal samples from seven independent expression data sets to provide a better view on the interactions between different transcription factors (TFs) and the most affected biological pathways in pancreatic cancer. We highlighted common differentially expressed genes (DEGs) and common affected processes within pancreatic cancer samples. We revealed 16 main DE-TFs that regulated gene expression alterations as well as the most significant processes in pancreatic cancer compared to normal cells. For example, we found the upregulated FOXM1 to be a top regulator of pancreatic cellular transformation based on results from different analyses, including from its regulation of gene regulatory networks, its presence in protein complex, its significant regulation of genes related to cancer pathways, and its regulation of most of the identified DE-TFs. Furthermore, we provided a model and assessed the role of different DE-TFs in the regulation of the most affected pancreatic- and cancer-specific processes. In conclusion, our bioinformatics meta-analysis of high throughput expression data sets, besides clarifying common affected genes and pathways, also showed the mechanisms involved in regulating these common profiles. Our results, especially for DE-TFs, could potentially be useful for screening for pancreatic cancer, and for confirming or determining novel pharmacological targets. J. Cell. Biochem. 118: 3976-3985, 2017. © 2017 Wiley Periodicals, Inc.

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Concepts to Target MYC in Pancreatic Cancer

Cited by 66 publications

References 84 publications

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

Identification of novel genes associated with a poor prognosis in pancreatic ductal adenocarcinoma via a bioinformatics analysis

Myc instructs and maintains pancreatic adenocarcinoma phenotype

Comprehensive Dissection of Transcriptome Data and Regulatory Factors in Pancreatic Cancer Cells

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