PXD053200-1

PXD053200 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 MECOM /SPINK1-/EGFR signaling
Description	The presence of noncanonical open reading frames within lncRNAs suggests their potential for translation, yielding various functional peptides or proteins. However, the existence and specific roles of these products in gastric cancer remain largely unexplored. Here we identify the HOXA10-HOXA9-derived small protein (HDSP) in gastric cancer through comprehensive analysis and experimental validation, including mass spectrometry and western blotting. HDSP exhibits high expression and oncogenic roles in gastric cancer. Mechanistically, HDSP blocks TRIM25-mediated ubiquitination and degradation by interacting with MECOM, leading to MECOM accumulation and enhanced SPINK1 transcription-a gene promoting cancer via the EGFR signaling pathway. Furthermore, MECOM fosters HOXA10-HOXA9 transcription, establishing a feedback loop activating SPINK1-EGFR signaling. HDSP knockdown inhibits tumor growth in a PDX model, and infusion of an artificially synthesized HDSP peptide as a neoantigen enhances immune cell-mediated anti-tumor efficacy against gastric cancer in vitro and in vivo. These findings propose HDSP as a potential therapeutic target or neoantigen candidate for gastric cancer treatment.
HostingRepository	PRIDE
AnnounceDate	2024-06-18
AnnouncementXML	Submission_2024-06-18_05:47:54.506.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guo Jiahao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-06-18 05:30:30	ID requested
⏵ 1	2024-06-18 05:47:54	announced

Dataset with its publication pending

submitter keyword: gastric cancer，EGFR signaling,novel microprotein

Ming Sun
contact affiliation	The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School
contact email	summing348@hotmail.com
lab head
Guo Jiahao
contact affiliation	nanjing Medical university
contact email	13675227002@163.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053200
     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 MECOM /SPINK1-/EGFR signaling