PXD066322-1

PXD066322 is an original dataset announced via ProteomeXchange.

Title	ZDHHC9 Promotes Osteosarcoma Progression via KRAS-Associated Enhancement of the RAS/MAPK Signaling Pathway
Description	Background: Osteosarcoma, a primary malignant bone tumor predominantly affecting children and adolescents, exhibits a dismal prognosis for patients with metastatic or recurrent disease, characterized by low five-year survival rates. This poor outcome is largely attributed to the incomplete understanding of the molecular mechanisms governing osteosarcoma aggressiveness and metastasis, coupled with a paucity of effective early diagnostic biomarkers and targeted therapeutic strategies. Consequently, elucidating the critical molecular events driving osteosarcoma pathogenesis and identifying novel biomarkers are of paramount importance for improving patient outcomes. Prior research has demonstrated aberrant expression of Zinc Finger DHHC-Type Palmitoyltransferase 9 (ZDHHC9) in various malignancies, but its specific function and clinical significance in osteosarcoma remain poorly defined. Methods: This study employed a comprehensive approach integrating bioinformatic analyses and experimental validation to investigate the functional role and clinical relevance of ZDHHC9 in osteosarcoma. Bioinformatic analyses (TIMER, GEPIA, TCGA databases) were utilized to examine ZDHHC9 expression across a pan-cancer landscape and its association with survival in osteosarcoma patients. Immunohistochemistry (IHC) and Western blotting were employed to analyze ZDHHC9 expression in clinical osteosarcoma specimens and cell lines. In vitro assays (CCK-8, colony formation, wound healing, Transwell, flow cytometry, and Western blotting) were performed to evaluate the impact of ZDHHC9 on osteosarcoma cell proliferation, migration, and invasion. Proteomic sequencing, molecular docking, and co-immunoprecipitation (Co-IP) experiments were conducted to explore the interaction between ZDHHC9 and KRAS. Western blotting was used to analyze the regulation of Raf1, ERK1/2, and p-ERK1/2 expression by ZDHHC9 and KRAS. Finally, a xenograft model was employed to assess the effect of ZDHHC9 on in vivo tumor growth. Results: Bioinformatic analyses revealed that elevated ZDHHC9 expression correlates with poor prognosis in osteosarcoma. IHC and Western blotting confirmed significantly increased ZDHHC9 expression in osteosarcoma tissues compared to adjacent non-tumorous tissues. Upregulation of ZDHHC9 was significantly associated with elevated Ki67 levels and advanced Enneking stage, suggesting a link to tumor aggressiveness. In vitro studies demonstrated that downregulation of ZDHHC9 suppressed osteosarcoma cell proliferation, migration, and invasion, while promoting apoptosis. Conversely, upregulation of ZDHHC9 elicited opposite effects. Proteomic sequencing revealed that ZDHHC9 knockdown significantly downregulated the expression of proteins associated with the RAS/MAPK signaling pathway. Functional experiments showed that overexpression of KRAS partially abrogated the inhibitory effects of ZDHHC9 knockdown on cell proliferation, migration, and invasion. Molecular docking and Co-IP experiments confirmed a specific interaction between ZDHHC9 and KRAS, leading to activation of the RAS/MAPK signaling pathway. Conclusion: ZDHHC9 promotes osteosarcoma cell proliferation, migration, and invasion by enhancing KRAS-mediated activity of the RAS/MAPK signaling pathway, which promotes cell cycle progression while inhibiting apoptosis.
HostingRepository	PRIDE
AnnounceDate	2025-10-27
AnnouncementXML	Submission_2025-10-26_17:11:51.398.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	志翔 李
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-18 20:38:11	ID requested
⏵ 1	2025-10-26 17:11:52	announced

10.1038/s41598-025-13787-6;

Li Z, Li J, Wu Y, Luo Y, Zheng J, Shi J, ZDHHC9 promotes osteosarcoma progression via KRAS-associated enhancement of the RAS/MAPK signaling pathway. Sci Rep, 15(1):35780(2025) [pubmed]

submitter keyword: MAPK pathway,ZDHHC9, proliferation, osteosarcoma, KRAS

Jiandang Shi
contact affiliation	Department of Orthopaedics, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
contact email	Shi_jiandang@nxmu.edu.cn
lab head
志翔 李
contact affiliation	Ningxia Medical University: Yinchuan, Ningxia, CN
contact email	lizhixiangnice@163.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/2025/10/PXD066322

PRIDE project URI

• PRIDE
  1. PXD066322
     1. Label: PRIDE project
     2. Name: ZDHHC9 Promotes Osteosarcoma Progression via KRAS-Associated Enhancement of the RAS/MAPK Signaling Pathway