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Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

ABSTRACT: Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

PROVIDER: PRJNA1089607 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28389652_1.fastq.gz	Fastqsanger.gz
	SRR28389652_2.fastq.gz	Fastqsanger.gz
	SRR28389653_1.fastq.gz	Fastqsanger.gz
	SRR28389653_2.fastq.gz	Fastqsanger.gz
	SRR28389654_1.fastq.gz	Fastqsanger.gz

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Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

Project description:Pathological role and the mechanism of psychological stress in cancer progression are little known. Here, we show in a mouse model that psychological stress drives pancreatic ductal adenocarcinoma (PDAC) progression via stimulating tumor nerve innervation. We demonstrate that nociception and other stressors activate sympathetic nerve to release Noradrenaline, downregulating tumor cell RNA demethylase alkB homolog 5 (Alkbh5). Alkbh5 deficiency causes cancer cell aberrant m6A modification of RNAs, which are packed to extracellular vesicles and delivered to neurons in the tumor microenvironment, enhancing hyperinnervation and PDAC progression. ALKBH5 levels are reversely correlated with tumor innervation and survival time in PDAC patients. Animal experiments identify a natural flavonoid Fisetin preventing neurons from taking in m6A-RNA contained EVs and suppress PDAC tumor excessive innervation and progression. Together, our study shed light on a novel molecular mechanism for neuro-cancer crosstalk linking psychological stress and cancer progression and raise a potential strategy for PDAC therapy.

2025-03-26 | GSE261937 | GEO

Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

2025-03-26 | GSE261936 | GEO

Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

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Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

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Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

Project description:Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

| PRJNA1010331 | ENA

Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

Project description:Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

| PRJNA1168575 | ENA

Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

Project description:Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer progression via extracellular vesicle transfer of m6A-modified RNAs

| PRJNA1089606 | ENA

ALKBH5 is a New Mammalian RNA Demethylase

Project description:N6-methyladenosine (m6A) is the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Here we report ALKBH5 as a new mammalian demethylase that oxidatively removes the m6A modification in mRNA in vitro and inside cells. This demethylation activity of ALKBH5 significantly affects mRNA export and RNA metabolism as well as the assembly of mRNA processing factors in nuclear speckles. Alkbh5-deficient male mice are characterized by impaired fertility resulting from apoptosis that affects meiotic metaphase-stage spermatocytes. In accordance with this defect, we have identified in mouse testes 1552 differentially expressed genes which cover broad functional categories and include spermatogenesis-related mRNAs involved in the p53 functional interaction network. We show that Alkbh5-deficiency impacts the expression levels of some of these mRNAs, supporting the observed phenotype. The discovery of this new RNA demethylase strongly suggests that the reversible m6A modification plays fundamental and broad functions in mammalian cells. RNA-seq in two cell types

2013-02-15 | E-GEOD-40132 | biostudies-arrayexpress

Mouse KPC cell secreted extracellular vesicle LC-MSMS

Project description:For Mouse KPC cell secreted extracellular vesicle LC-MSMS, extracellular vesicles in Alkbh5-WT or Alkbh5-KO KPC cell culture medium were isolated by ultracentrifugation. The protein and its levels in extracellular vesicle were determined through LC-MSMS.

2025-03-26 | PXD061967 | Pride

ALKBH5

Project description:ALKBH5

| PRJNA932008 | ENA