PXD072167-1

PXD072167 is an original dataset announced via ProteomeXchange.

Title	DICER1 syndrome-associated mutations lead to 3p-miRNA gain of function and increased metastatic potential
Description	The DICER1 gene is mutated in cancer, including Dicer1 syndrome, a rare tumour predisposition syndrome. Cancer-associated hotspots mutations have been reported in both catalytic domains of Dicer, and are predicted to disrupt miRNA processing activity. To understand these hotspot mutations in cancer development, we have generated cell lines harbouring single amino acid substitutions within either the RNAse IIIa (S1344L) and the RNAse IIIb (D1709N) domains of the endogenous Dicer1 gene. We show that both mutations result in a widespread loss of 5p miRNAs, but, unexpectedly, an increase in 3p passenger strands loading into Ago2. Similarities between both mutants can be explained as the S1344 residue is structurally also part of the RNase IIIb catalytical site. Functionally, we found that changes in the repertoire of miRNAs loaded into Ago2 result in altered gene expression, impacting critical pathways for cancer development, including metastatic potential. Our results indicate that inactivating the processing activity of Dicer does not result in genomic instability. Instead, mutations cause a specific upregulation of human endogenous retrovirus H (HERVH) and 3p miRNAs, which have the potential to be used as markers for Dicer1 syndrome tumours.
HostingRepository	PRIDE
AnnounceDate	2026-06-23
AnnouncementXML	Submission_2026-06-23_07:42:19.855.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christos Spanos
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-18 16:15:31	ID requested
⏵ 1	2026-06-23 07:42:20	announced

Dataset with its publication pending

submitter keyword: cancer, DIA,DICER1, mutations, Exploris480

Sara Macias Ribela
contact affiliation	University of Edinburgh
contact email	Sara.Maciasribela@ed.ac.uk
lab head
Christos Spanos
contact affiliation	University of Edinburgh
contact email	spanos.christos@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD072167
     1. Label: PRIDE project
     2. Name: DICER1 syndrome-associated mutations lead to 3p-miRNA gain of function and increased metastatic potential