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PXD026949

PXD026949 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMinor intron splicing efficiency increases with the development of lethal prostate cancer
DescriptionMinor intron-containing genes (MIGs) are crucial cell cycle regulators and are essential for cell survival. Thus, we explored whether MIGs play a role in cancer progression and cancer therapy resistance. Here we show that MIG-expression segregates sensitive and resistant prostate cancer cells from each other and them from benign tissue. Moreover, the rate of minor intron splicing, a crucial regulatory node for MIG-expression, was more efficient in patients with advanced prostate cancer. We show that the increased minor spliceosome (MiS) activity is downstream of the androgen receptor signaling axis in both therapy sensitive and insensitive prostate cancer types. The increased MiS activity was in line with the elevated expression of U6atac snRNA, a crucial MiS component. We propose the expression of U6atac as a potential point of vulnerability in cancer. MIGs are uniquely susceptible to the MiS, so we used siRNA against ­U6atac, which like protein-coding transcripts, is downregulated. Inhibition of MiS was sufficient to lower the tumor burden significantly in therapy-resistant (prostate) cancer cells and PCa patient-derived organoids. KD cells displayed elevated minor intron retention and alternative splicing across minor introns of  MIGs which enriched for MAPK activity, DNA repair and cell cycle regulation. Importantly, these findings were confirmed by MassSpec analysis. Collectively our study nominates the MiS as a driver of highly proliferative, rapidly dividing (prostate) cancer cells that bears strong potential as a therapeutic target for many different cancer types.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:47:23.790.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterManfred Heller
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-06-27 15:50:51ID requested
12023-06-08 10:32:08announced
22023-11-14 09:01:02announced2023-11-14: Updated project metadata.
32024-10-22 05:47:24announced2024-10-22: Updated project metadata.
Publication List
10.1016/J.MOLCEL.2023.05.017;
Keyword List
submitter keyword: minor spliceosome, lineage plasticity, minor intron genes, U6atac,Prostate cancer
Contact List
Mark A. Rubin
contact affiliationDepartment for BioMedical Research (DBMR) University of Bern Murtenstrasse 35 3008 Bern Switzerland
contact emailmark.rubin@dbmr.unibe.ch
lab head
Manfred Heller
contact affiliationProteomics and Mass Spectrometry Core Facility, Department for BioMedical Research (DBMR), University of Bern, Bern, Switzerland
contact emailpmscf@dbmr.unibe.ch
dataset submitter
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