PXD043737-1

PXD043737 is an original dataset announced via ProteomeXchange.

Title	A novel microprotein HDSP encoded by HOXA10-HOXA9 triggers progression of gastric cancer through maintaining the stability of MECOM and activating SPINK1-EGFR signaling
Description	The abundance of noncanonical open reading frames present in long noncoding RNAs (lncRNAs) indicates the potential for translational capacity, thereby enabling the generation of multiple functional peptides or proteins. Nevertheless, the existence of peptide or protein products derived from lncRNAs and their specific roles in gastric cancer remain largely unexplored. In this study, we identified HOXA10-HOXA9-derived small protein (HDSP) in gastric cancer by conducting a comprehensive analysis and experimental validation with mass spectrometry and western blotting. HDSP is highly expressed and has oncogenic roles in gastric cancer. Mechanistically, HDSP blocked TRIM25-mediated ubiquitination and degradation by interacting with MECOM. This led to the accumulation of MECOM, which further enhanced the transcription of SPINK1, a gene that promotes cancer through the EGFR signaling pathway. In addition, MECOM promoted the transcription of HOXA10-HOXA9, creating a feedback regulatory loop that activated downstream SPINK1-EGFR signaling. Finally, we found that HDSP knockdown inhibited tumor growth in a patient-derived xenograft (PDX) model, and the infusion of an artificially synthesized HDSP peptide as a neoantigen improved the anti-tumor efficacy of immune cells against gastric cancer in vitro and in vivo. Our findings provide a potential therapeutic target or neoantigen candidate for the treatment of gastric cancer.
HostingRepository	PRIDE
AnnounceDate	2024-05-07
AnnouncementXML	Submission_2024-05-07_06:44:52.175.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ming Sun
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-12 20:04:42	ID requested
⏵ 1	2024-05-07 06:44:52	announced
2	2024-10-22 06:38:21	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human，Gastric cancer，LC-MSMS

Sun Ming
contact affiliation	The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Baita west road #16, Suzhou 215001, China.
contact email	sunming348@hotmail.com
lab head
Ming Sun
contact affiliation	The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University
contact email	sunming348@hotmail.com
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/2024/05/PXD043737

PRIDE project URI

• PRIDE
  1. PXD043737
     1. Label: PRIDE project
     2. Name: A novel microprotein HDSP encoded by HOXA10-HOXA9 triggers progression of gastric cancer through maintaining the stability of MECOM and activating SPINK1-EGFR signaling