PXD035928-2

PXD035928 is an original dataset announced via ProteomeXchange.

Title	The spliceosome factor USP39 promotes hepatocellular carcinoma malignancy through regulating mRNA splicing
Description	Abnormal alternative splicing (AS) caused by alterations to splicing factors contributes to tumor progression. Nonetheless, the relevant targets and mechanisms remain elusive in hepatocellular carcinoma (HCC). Here, we reported that overexpression of Ubiquitin-specific protease 39 (USP39), a spliceosome component of the U4/U6.U5 tri-snRNP complex, is associated with poor clinical outcomes and proliferative signaling. Functionally, hepatocyte-specific USP39 knockin mice exhibited enhanced hepatocarcinogenesis. In vitro, USP39 promoted HCC cell proliferation and cell cycle progression in a spliceosome-dependent manner. Transcriptomic analysis revealed that USP39 depletion led to comprehensively impaired constitutive splicing and intriguingly, selective AS of hundreds of genes. USP39-mediated splicing switch of KANK2-S to KANK2-L increased the tumorigenic potential of HCC cells through accelerating KANK2 translation. Mechanistically, USP39 modulates exon inclusion/exclusion via interaction with SRSF6 or hnRNPC in a position-dependent manner. These findings highlight a role for USP39 as a splicing regulator in HCC biology and establishing its position-dependent splicing model.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:06:52.448.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yan Li
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-10 09:01:15	ID requested
1	2023-10-24 10:59:12	announced
⏵ 2	2023-11-14 09:06:58	announced	2023-11-14: Updated project metadata.
3	2024-10-22 06:08:22	announced	2024-10-22: Updated project metadata.

Zheng J, Wu S, Tang M, Xi S, Wang Y, Ren J, Luo H, Hu P, Sun L, Du Y, Yang H, Wang F, Gao H, Dai Z, Ou X, Li Y, USP39 promotes hepatocellular carcinogenesis through regulating alternative splicing in cooperation with SRSF6/HNRNPC. Cell Death Dis, 14(10):670(2023) [pubmed]

submitter keyword: alternative splicing

KANK2

SRSF6

HNRNPC

constitutive splicing

Yan Li
contact affiliation	Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China
contact email	liy33@sustech.edu.cn
lab head
Yan Li
contact affiliation	Southern University of Science and Technology
contact email	liy33@sustech.edu.cn
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD035928

PRIDE project URI

• PRIDE
  1. PXD035928
     1. Label: PRIDE project
     2. Name: The spliceosome factor USP39 promotes hepatocellular carcinoma malignancy through regulating mRNA splicing