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DDX5 super-enhancer promote vasculogenic mimicry formation and metastasis in nasopharyngeal carcinoma by enhancing ADAM10 transcription

ABSTRACT: DDX5 super-enhancer promote vasculogenic mimicry formation and metastasis in nasopharyngeal carcinoma by enhancing ADAM10 transcription

PROVIDER: PRJNA1096631 | ENA |

REPOSITORIES: ENA

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			Action	DRS
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	SRR28563554_1.fastq.gz	Fastqsanger.gz
	SRR28563554_2.fastq.gz	Fastqsanger.gz

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DDX5 super-enhancer promote vasculogenic mimicry formation and metastasis in nasopharyngeal carcinoma by enhancing ADAM10 transcription

Project description:Antiangiogenetic therapies (AATs) have limited effects owing to most patients with cancer inevitably developing resistance to them. In this study, data generated using a nasopharyngeal carcinoma orthotopic mouse model in combination with clinical data suggested compensatory vasculogenic mimicry (VM) formation during AATs and the association of VM with poor prognosis of nasopharyngeal carcinoma. Additionally, data-independent acquisition mass spectrometry-based proteomics demonstrated that ADAM10 upregulation contributes to VM. Mechanistically, epigenetic and high-resolution chromatin interaction landscape analyses revealed that while ADAM10 does not interact with either the proximal or distal enhancers, DDX5, a transcription factor of ADAM10, is regulated by long-range looping enhancer-promoter interactions. Further analysis identified transcription factors bound to critical constituents of the DDX5 super-enhancer. Ingenol Mebutate, which docked excellently with DDX5, reversed ADAM10-mediated changes in gene expression, thereby effectively suppressing compensatory VM formation and metastasis and improving prognosis. Collectively, these findings provide insights into the clinical application of AATs.

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DDX5 super-enhancer promote vasculogenic mimicry formation and metastasis in nasopharyngeal carcinoma by enhancing ADAM10 transcription

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DDX5 super-enhancer promote vasculogenic mimicry formation and metastasis in nasopharyngeal carcinoma by enhancing ADAM10 transcription

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