PXD073999-1

PXD073999 is an original dataset announced via ProteomeXchange.

Title	Mechanisms of the antiproliferative effects of SIRT6 inhibition in melanoma: A multi-omics analysis
Description	Background/Objectives: Melanoma is one of the deadliest types of skin cancer due to its ability to metastasize if not treated early. While targeted- and immune- therapies have significantly improved melanoma treatment outcomes, acquired drug resistance even with combined therapeutics remain prevalent. SIRT6 is a nuclear histone deacetylase that regulates DNA repair, metabolism, and chromatin remodeling. It is overexpressed in melanoma and its inhibition in melanoma is known to have anti-proliferative response, and alterations in pathways related to cell cycle, senescence, and metastasis. Methods: To deepen our understanding of the role of SIRT6 in melanoma, in this study we utilized RNA sequencing, proteomics, and Ingenuity Pathway Analysis on genetically modified human melanoma cells to determine the downstream mechanism of SIRT6 in melanoma. Results: SIRT6 knock down (KD) in A375 and G361 melanoma cells, with CRISPR/Cas9 or shRNA techniques, resulted in a significant decrease in proliferation and clonogenic survival of the cells. SIRT6 KD caused an altered expression of multiple genes associated with cell proliferation, mitotic regulation, invasion, cell death/senescence, and immunomodulation, including AURKB, ANLN, MYC, FOXM1, RABL6, E2F2, TP53, RBL1, OSM, TNF, IL1B, IL6 and IFNG. Comparative analysis at both transcription and translation levels revealed coordinated downregulation of proliferation, invasion, and migration and upregulation of targets related to cell death, apoptosis, and necrosis. Multi-omics analysis also predicted downregulation of signaling networks associated with MAP3K20, MYC, MKNK, and HMGCR. Conclusions: Given its involvement in tumorigenesis, this study underlines the importance of SIRT6 in melanoma and provides support to its potential as a novel therapeutic target for melanoma.
HostingRepository	PRIDE
AnnounceDate	2026-03-30
AnnouncementXML	Submission_2026-03-29_16:06:43.437.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mary Ndiaye
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	2026-02-03 12:49:53	ID requested
⏵ 1	2026-03-29 16:06:44	announced

Anaya Aldrete KB, Muntaqua D, Garcia-Peterson LM, Ndiaye MA, Nam JH, Ahmad N, Mechanisms of the Antiproliferative Effects of SIRT6 Inhibition in Melanoma: A Multi-Omics Analysis. Cancers (Basel), 18(4):(2026) [pubmed]

10.3390/cancers18040590;

submitter keyword: Human, Melanoma, SIRT6

Nihal Ahmad
contact affiliation	Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA
contact email	nahmad@dermatology.wisc.edu
lab head
Mary Ndiaye
contact affiliation	University of Wisconsin-Madison
contact email	mndiaye@dermatology.wisc.edu
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/2026/03/PXD073999

PRIDE project URI

• PRIDE
  1. PXD073999
     1. Label: PRIDE project
     2. Name: Mechanisms of the antiproliferative effects of SIRT6 inhibition in melanoma: A multi-omics analysis