PXD059596-1

PXD059596 is an original dataset announced via ProteomeXchange.

Title	Inhibition of tumor-intrinsic NAT10 enhances antitumor immunity by triggering type I interferon responses via MYC/CDK2/DNMT1 pathway
Description	Posttranscriptional modifications are deeply involved in cancer progression; however, there remains knowledge gap regarding the function and immune regulatory mechanism of newly discovered mRNA acetylation modification. Here, we discovered an unexpected role of N4-acetylcytidine (ac4C) RNA acetyltransferase NAT10 in reshaping the tumor immune microenvironment. By analyzing patients' data, we found that NAT10 was upregulated in tumor tissues and negatively correlated with immune cell infiltration and overall survival. Loss of tumoral NAT10 significantly stimulated tumor-specific cellular immune responses and suppressed tumor growth. Mechanistically, we identified MYC as a key downstream target of NAT10 via enhancing mRNA stability and translation efficiency. Inhibition of NAT10 blocked the MYC/CDK2/DNMT1 pathway, subsequently enhancing double-stranded RNAs (dsRNA) formation, which triggered type I interferon responses to enhance the in vivo response of tumor specific CD8+ T cells. More importantly, inhibition of NAT10 using either small molecule inhibitor (Remodelin) or PEI/PC7A/siNAT10 nanoparticles combined with PD-1 blockade synergistically enhanced the anti-tumor immune response and repressed tumor progression. Our findings uncovered the crucial role of tumor-intrinsic NAT10 in tumor immune microenvironment, representing a promising target for enhancing cancer immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2025-05-16
AnnouncementXML	Submission_2025-05-16_00:37:38.548.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wancheng Liu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-09 07:50:13	ID requested
⏵ 1	2025-05-16 00:37:38	announced

Dataset with its publication pending

submitter keyword: N-acetyltransferase 10

Type I IFN

CD8+ T cell

Immunotherapy.

Wancheng Liu
contact affiliation	Qilu Hospital of Shandong University
contact email	LWC15190@gmail.com
lab head
Wancheng Liu
contact affiliation	qilu hospital of Shandong university
contact email	LWC15190@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059596
     1. Label: PRIDE project
     2. Name: Inhibition of tumor-intrinsic NAT10 enhances antitumor immunity by triggering type I interferon responses via MYC/CDK2/DNMT1 pathway