PXD010342-2

PXD010342 is an original dataset announced via ProteomeXchange.

Title	Inhibition of histone methyltransferase EZH2 in Schistosoma mansoni by GSK343 decreases the expression of genes implicated in DNA replication and ncRNA metabolism
Description	Schistosomiasis is a chronic and debilitating disease caused by a trematode of the genus Schistosoma. The current strategy for the control of the disease involves treatment with Praziquantel, the only available drug. The development of new drugs is therefore a top priority. Drugs that inhibit histone modifying enzymes have been used in cancer, altering gene expression, replication, repair and DNA recombination. Schistosoma parasites have some characteristics similar to malignant tumors, such as intense cell division and high levels of metabolic activity. Here we evaluate in Schistosoma mansoni the effect of GSK343, an inhibitor of the histone methyltransferase EZH2 that had been shown to arrest or reduce the growth of human cancer cells. We show that GSK343 causes damage to the parasite tegument and reduces egg laying in vitro, concomitant with a decrease in levels of H3K27me3, the histone mark put in place by EZH2. RNA-seq and proteomic analyses of treated parasites showed changes in the expression of hundreds of genes involved in important metabolic processes. In females, a marked decrease was observed in the expression of genes related to processes such as DNA replication and noncoding RNA metabolism. In conclusion, the histone methyltransferase EZH2 seems to be a promising novel drug target against schistosomiasis.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:40:34.169.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Pires
SpeciesList	scientific name: Schistosoma mansoni (Blood fluke); NCBI TaxID: 6183;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-09 08:22:40	ID requested
1	2018-11-23 06:59:46	announced
⏵ 2	2024-10-22 04:40:36	announced	2024-10-22: Updated project metadata.

10.1371/journal.pntd.0006873;

Pereira ASA, Amaral MS, Vasconcelos EJR, Pires DS, Asif H, daSilva LF, Morales-Vicente DA, Carneiro VC, Angeli CB, Palmisano G, Fantappie MR, Pierce RJ, Setubal JC, Verjovski-Almeida S, Inhibition of histone methyltransferase EZH2 in Schistosoma mansoni in vitro by GSK343 reduces egg laying and decreases the expression of genes implicated in DNA replication and noncoding RNA metabolism. PLoS Negl Trop Dis, 12(10):e0006873(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: proteomics, Schistosoma mansoni, EZH2,GSK343, RNA-seq

Sergio Verjovski-Almeida
contact affiliation	Instituto de Química da Universidade de São Paulo Instituto Butantan
contact email	verjo@iq.usp.br
lab head
David Pires
contact affiliation	Instituto Butantan
contact email	david.pires@butantan.gov.br
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD010342
     1. Label: PRIDE project
     2. Name: Inhibition of histone methyltransferase EZH2 in Schistosoma mansoni by GSK343 decreases the expression of genes implicated in DNA replication and ncRNA metabolism