PXD065389

PXD065389 is an original dataset announced via ProteomeXchange.

Title	An SRRM3 regulated neural alternative splicing program is subverted to promote tumour progression in pancreatic neuroendocrine cells.
Description	Pancreatic neuroendocrine tumours (PanNETs) are a heterogeneous group of neoplasms arising in pancreatic islets and altering the hormone secreting function of neuroendocrine cells. Genome wide approaches have revealed the genomic landscape of PanNETs but have not explained their problematic hormone secretion. We show here that alternative splicing (AS) deregulation is responsible for changes in the secretory ability of PanNET cells. We reveal that the RNA binding protein SRRM3 is upregulated in PanNETs and favours the inclusion of a group of alternative microexons in certain mRNAs. These microexons are part of a larger neural program regulated by SRRM3 and their inclusion results in protein isoforms that change stimulus-induced insulin trafficking and secretion. By downregulating SRRM3 or inhibiting its binding on three of the microexon bearing pre-mRNAs, in animal and cellular PanNET models, we prove the necessity of SRRM3 for hormone secretion, PanNET progression and the enhanced neural component of PanNET tumours.
HostingRepository	PRIDE
AnnounceDate	2025-08-08
AnnouncementXML	Submission_2025-08-08_08:51:40.289.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Martina Samiotaki
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-24 04:05:59	ID requested
⏵ 1	2025-08-08 08:51:40	announced

10.1016/J.CELREP.2025.116022;

submitter keyword: alternative splicing, microexons, pancreatic neuroendocrine tumours, insulin secretion, SRRM3

Panagiota Kafasla
contact affiliation	B.S.R.C. “Alexander Fleming”, Vari, Athens, Greece
contact email	kafasla@fleming.gr
lab head
Martina Samiotaki
contact affiliation	Protein Analysis Laboratory B.S.R.C. "Alexander Fleming", Alexander Fleming Street 34 16672, Vari, Greece
contact email	samiotaki@fleming.gr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD065389
     1. Label: PRIDE project
     2. Name: An SRRM3 regulated neural alternative splicing program is subverted to promote tumour progression in pancreatic neuroendocrine cells.