PXD041853-3

PXD041853 is an original dataset announced via ProteomeXchange.

Title	Inhibition of nonsense-mediated mRNA decay reduces the tumorigenicity of human fibrosarcoma cells
Description	Nonsense-mediated mRNA decay (NMD) is a eukaryotic RNA degradation pathway that targets for degradation faulty mRNAs with premature termination codons as well as many physiological mRNAs encoding full-length proteins. Consequently, NMD functions in both, quality control and post-transcriptional regulation of gene expression, and it has been implicated in the modulation of cancer progression. To investigate the role of NMD in cancer, we knocked out SMG7 in the HT1080 human fibrosarcoma cell line. SMG7 is involved in deadenylation-coupled exonucleolytic mRNA decay, one of the two main degradation pathways in mammalian NMD. Genome-wide proteomic and transcriptomic analyses confirmed that NMD is severely compromised in these SMG7-knockout HT1080 cells. We compared the oncogenic properties between the parental, the SMG7-knockout, and a rescue cell line in which we re-introduced both isoforms of SMG7. In parallel, we tested the effect of a drug inhibiting the NMD factor SMG1 on the HT1080 cells to distinguish NMD-dependent effects from putative NMD-independent functions of SMG7. Using cell-based assays as well as a mouse xenograft tumor model, we show that the oncogenic properties of the parental HT1080 cells areseverely compromised when NMD is inhibited. Molecular pathway analysis revealed a strong reduction of the matrix metalloprotease 9 (MMP9) gene expression in NMD-suppressed cells. Since MMP9 expression promotes cancer cell migration and invasion, metastasis and angiogenesis, its downregulation in NMD-suppressed cells explains, at least partially, their reduced tumorigenicity. Collectively, our findings emphasize the therapeutic potential of NMD inhibition for the treatment ofcertain types of cancer.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:03:23.497.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Manfred Heller
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-04-27 08:35:00	ID requested
1	2023-09-19 05:47:53	announced
2	2023-11-14 09:02:16	announced	2023-11-14: Updated project metadata.
⏵ 3	2024-10-22 06:03:23	announced	2024-10-22: Updated project metadata.

10.1093/NARCAN/ZCAD048;

submitter keyword: SMG7,NMD, cell migration, fibrosarcoma, tumor progression

Oliver Mühlemann
contact affiliation	Dept. of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Switzerland
contact email	oliver.muehlemann@unibe.ch
lab head
Manfred Heller
contact affiliation	Proteomics and Mass Spectrometry Core Facility, Departement for Biomedical Research, University of Berne
contact email	pmscf.dbmr@unibe.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041853
     1. Label: PRIDE project
     2. Name: Inhibition of nonsense-mediated mRNA decay reduces the tumorigenicity of human fibrosarcoma cells