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ABSTRACT: Senescence-induced vascular remodeling creates new therapeutic vulnerabilities in pancreas cancer

PROVIDER: PRJNA607826 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11127466_1.fastq.gz	Fastqsanger.gz
	SRR11127466_2.fastq.gz	Fastqsanger.gz
	SRR11127467_1.fastq.gz	Fastqsanger.gz
	SRR11127467_2.fastq.gz	Fastqsanger.gz
	SRR11127468_1.fastq.gz	Fastqsanger.gz

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Senescence-induced vascular remodeling creates therapeutic vulnerabilities in pancreas cancer

Project description:Senescence-induced vascular remodeling creates therapeutic vulnerabilities in pancreas cancer

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SETD2 Loss Creates A Permissive Epigenetic Landscape that Promotes Kidney Cancer Metastasis and Engenders Therapeutic Vulnerabilities

Project description:SETD2 Loss Creates A Permissive Epigenetic Landscape that Promotes Kidney Cancer Metastasis and Engenders Therapeutic Vulnerabilities

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Endothelial OTUD1 promotes Ang II-induced vascular remodeling by deubiquitinating SMAD3

Project description:Understanding the molecular mechanisms of pathological vascular remodeling is important for treating cardiovascular diseases and complications. Recent studies have highlighted a role of deubiquitinases in vascular pathophysiology. In this study, we investigated the role of a deubiquitinase, OTUD1, in angiotensin II (Ang II)-induced vascular remodeling. We identified upregulated OTUD1 in the vascular endothelium of Ang II-challenged mice and showed OTUD1 deletion attenuated vascular remodeling, collagen deposition, and EndMT. Conversely, OTUD1 overexpression aggravated these pathological changes both in vivo and in vitro. Mechanistically, SMAD3 was identified as a substrate of OTUD1 using co-immunoprecipitation followed with LC-MS/MS. We found OTUD1 stabilizes SMAD3 and facilitates SMAD3/SMAD4 complex formation and subsequent nuclear translocation through both K48- and K63-linked deubiquitination. OTUD1-mediated SMAD3 activation regulate the transcription of genes involved in vascular EndMT and remodeling in HUVECs. Finally, SMAD3 inhibition reversed OTUD1-promoted vascular remodeling. Our findings demonstrate endothelial OTUD1 promoted Ang II-induced vascular remodeling by deubiquitinating SMAD3. This study identified SMAD3 as a target of OTUD1 and indicates OTUD1 as a potential therapeutic target for the diseases related to vascular remodeling.

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Endothelial senescence mediates hypoxia-induced vascular remodeling by modulating PDGFB expression

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Project description:The phenotypic switching of vascular smooth muscle cells (VSMCs) leads to neointimal hyperplasia, which is the underlying cause of vascular remodeling diseases such as atherosclerosis and hypertension. Novel hidden proteins encoded by circular RNAs (circRNAs) play crucial roles in disease progression. Our study identified a new protein derived from a circRNA in VSMCs and demonstrated its potential role in regulating vascular remodeling. We discovered a novel hidden protein, p-414aa, encoded by circSETD2(14,15), which can inhibit vascular remodeling. Both circSETD2(14,15) and p-414aa may serve as potential therapeutic targets for vascular remodeling diseases. In this study, we demonstrated that the new protein p-414aa encoded by circSETD2(14,15) inhibits VSMC proliferation and neointimal hyperplasia through the HuR/C-FOS axis. In summary, our data provide a molecular framework for the phenotypic switching of vascular smooth muscle cells.

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