PXD013334

PXD013334 is an original dataset announced via ProteomeXchange.

Title	Stress-induced lncRNA LAS3 fosters fitness of cancer cells by regulating SART3-mediated spliceosome recycling
Description	Long non-coding RNAs (lncRNAs) represent a novel class of anti-cancer therapeutic targets. Hypoxia-induced lncRNAs are associated with the aggressive tumor phenotypes and might serve as putative drug targets. Here, we unraveled lncRNAs whose expression is upregulated in hypoxic breast tumors. One of the hypoxia-induced lncRNA, LAS3 (LncRNA Associated to SART3), is commonly upregulated not only in all breast cancer subtypes, but also in several types of epithelial cancers. LAS3 expression is driven by the stress-induced JNK/c-JUN pathway, which is frequently activated in human cancer. By pull down of LAS3 coupled to mass spectrometry-based proteomics, we identified SART3, a component of the splicing machinery, as a LAS3-interacting partner. In a second proteomics experiment, pull down of SART3-containing complexes from MCF10A cells treated with either scramble, or LAS3-specific GapmeRs showed that LAS3 regulates splicing efficiency by triggering SART3 dissociation from the U4/U6 snRNP during the recycling phase of the spliceosome cycle. Finally, differential shotgun analysis of MDA-MB-231/tet-shLAS3 cells allowed us to quantify expression of 2,940 proteins. Here, genes with significant intron retention showed decreased protein expression levels, indicating that widespread LAS3-mediated intron retention disrupts open reading frame integrity leading to stochastic decrease of protein expression and decreased fitness of cancer cells. Together, our data show that LAS3 is essential for growth of LAS3-positive triple negative breast tumors and indicate that LAS3 inhibition might be a suitable therapeutic approach for breast cancer treatment.
HostingRepository	PRIDE
AnnounceDate	2020-05-26
AnnouncementXML	Submission_2020-05-26_14:00:49.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Impens Francis
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-04-01 08:09:52	ID requested
⏵ 1	2020-05-26 14:00:50	announced

De Troyer L, Zhao P, Pastor T, Baietti MF, Barra J, Vendramin R, Dok R, Lechat B, Najm P, Van Haver D, Impens F, Leucci E, Sablina AA, Stress-induced lncRNA LASTR fosters cancer cell fitness by regulating the activity of the U4/U6 recycling factor SART3. Nucleic Acids Res, 48(5):2502-2517(2020) [pubmed]

submitter keyword: long non-coding RNAs, breast cancer, hypoxia, SART3, intron retention

Anna Sablina
contact affiliation	VIB-KU Leuven Center for Cancer Biology, VIB, 3000 Leuven, Belgium; Department of Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
contact email	anna.sablina@kuleuven.vib.be
lab head
Impens Francis
contact affiliation	VIB Proteomics Core Ghent University
contact email	francis.impens@vib-ugent.be
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013334
     1. Label: PRIDE project
     2. Name: Stress-induced lncRNA LAS3 fosters fitness of cancer cells by regulating SART3-mediated spliceosome recycling