PXD054835-1

PXD054835 is an original dataset announced via ProteomeXchange.

Title	The disturbance of lipid metabolism by the TNF-α /PLEKHA5/FCRLA axis leads to the proliferation, invasion and metastasis of cutaneous malignant melanoma
Description	Background: Cutaneous malignant melanoma (CMM) is one of the most highly fatal cancers; its pathogenesis requires study. We recognize that abnormalities in lipid metabolism may be associated with the risk of CMM development; nevertheless, the role of lipid metabolism in the proliferation, invasion, and metastasis of CMM remains unclear. Methods: Lipid metabolism-related genes were identified in MsigDB. A lipid metabolism-related predictive model was constructed in TCGA-SKCM using univariate Cox regression analysis, consensus cluster analysis, WGCNA analysis, LASSO regression analysis, and outcomes-related genes were identified. Immunohistochemistry, qPCR, and western blotting were used to identify essential genes, construct stable lentivirus strains, and study the biological role of PLEKHA5 in CMM cells. Transcriptomic and proteomic sequencing, protein-protein molecular docking, CO-IP, and GST pull-down were performed on the cells with knockout essential genes to explore this gene’s upstream and downstream regulatory mechanisms. After analyzing the results of lipid metabolomics sequencing, the effects of the essential lipids related to CMM cells after the gene knockdown were studied. Results: A predictive model was established, Risk Score = -0.009 * UBE2L6 + 0.033 * PLEKHA5 + 0.024 * LHB + 0.036 * CARM1 + 0.016 * PRXL2B + 0.131 * PLA2G4D. PLEKHA5 was identified as an essential gene, and PLEKHA5 was positively correlated with poor outcomes in CMM patients. PLEKHA5 is more highly expressed than melanocytes in CMM, which promotes the proliferation, invasion, and metastasis of CMM. FCRLA is the downstream gene of PLEKHA5, upregulated in CMM, and the primary enrichment pathway is the TNFα-NFκB signaling pathway. TNFα is also an essential cytokine that promotes CMM proliferation and metastasis. Hex1Cer(d18:1/26:2) and Cer(d18:2/26:2) in the downstream were significantly decreased, while ChE(0:0), ChE(18:0) and TG(18:0/16:0/19:0) in the downstream were significantly increased. The cholesterol ester inhibitor avasimibe inhibits CMM proliferation, metastasis, and invasion. Conclusion: The predictive model of CMM related to lipid metabolism established in this study has good predictive ability. PLEKHA5 is an essential biomarker related to lipid metabolism in CMM. TNFα-PLEKHA5-FCRLA is a signal axis that promotes proliferation, metastasis, and invasion of CMM. Its downstream product, the cholesterol ester inhibitor avasimibe, may treat CMM.
HostingRepository	iProX
AnnounceDate	2024-08-12
AnnouncementXML	Submission_2024-08-12_21:02:06.361.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kexin Yan
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2024-08-12 21:01:48	ID requested
⏵ 1	2024-08-12 21:02:06	announced

Dataset with its publication pending

submitter keyword: Lipid metabolism

Cutaneous malignant melanoma

Oncogene

Risk model

Kexin Yan
contact affiliation	Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College
contact email	982194794@qq.com
lab head
Kexin Yan
contact affiliation	Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College
contact email	982194794@qq.com
dataset submitter

iProX dataset URI