PXD018104

PXD018104 is an original dataset announced via ProteomeXchange.

Title	The loss of the RNA helicase Dhx15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice
Description	DHX15 is an ATP-dependent RNA helicase involved in pre-mRNA splicing. We have recently reported that DHX15 is a downstream substrate for Akt1, which plays a significant role in vascular biology. Therefore, we aimed to explore the regulatory function of DHX15 over the vasculature, and the endothelial cell biology in different contexts: development, metabolism, ischemia and tumor growth. Methods: Deficient DHX15 mice and zebrafish were generated using transcription activator-like effector nuclease (TALEN) and Crispr/cas9 gene edition. Lymphatic functionality was evaluated by lymphangiography and magnetic resonance imaging. Mouse-induced tumor and metastasis model were generated by injection of syngeneic LLC1 tumor cells. DHX15 gene silencing in mouse liver endothelial cells (LEC) was performed by the lentiviral transduction of shRNA (Dharmacon). The changes in the transcriptome and the proteome resulting from the shRNA transduction were investigated by RNAseq and mass spectrometry, respectively. Results: Homozygous DHX15 gene deficiency was lethal in mouse and zebrafish embryos. DHX15-/- zebrafish also showed an undeveloped parachordal line, which leads to the formation of lymphatic structures in the trunk during the development. DHX15+/- mice and zebrafish were viable, although DHX15+/- gene deficiency triggered lower vascular network density and impaired lymphatic function postnatally in mice. Whole transcriptome and proteome analysis of DHX15 silenced LEC revealed differential expression of enzymes involved in the glycolysis and the gluconeogenesis pathways. The functional validation of these results demonstrated an uncoupling of the glycolysis with the oxidation of pyruvate into the mitochondria and lower activity of the Complex I in the mitochondrial membrane, resulting in lower cellular ATP production. Noteworthy, heterozygous DHX15 deficiency partially inhibited primary tumor growth and reduced lung metastasis after injection of syngeneic LLC1 tumor cells, compared to wild-type mice
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:30:14.183.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	guadalupe espadas
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-19 02:48:37	ID requested
1	2021-11-04 00:21:47	announced
⏵ 2	2024-10-22 05:30:15	announced	2024-10-22: Updated project metadata.

10.1038/s42003-021-02722-w;

Ribera J, Portol, é, s I, C, ó, rdoba-Jover B, Rodr, í, guez-Vita J, Casals G, Gonz, á, lez-de la Presa B, Graupera M, Solsona-Vilarrasa E, Garcia-Ruiz C, Fern, á, ndez-Checa JC, Soria G, Tudela R, Esteve-Codina A, Espadas G, Sabid, ó E, Jim, é, nez W, Sessa WC, Morales-Ruiz M, The loss of DHX15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice. Commun Biol, 4(1):1192(2021) [pubmed]

submitter keyword: LTQ-Orbitrap Fusion Lumos

Eduard Sabidó
contact affiliation	Centre for Genomic Regulation (CRG)
contact email	eduard.sabido@crg.eu
lab head
guadalupe espadas
contact affiliation	crg
contact email	guadalupe.espadas@crg.eu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD018104
     1. Label: PRIDE project
     2. Name: The loss of the RNA helicase Dhx15 impairs endothelial energy metabolism, lymphatic drainage and tumor metastasis in mice