PXD068724

PXD068724 is an original dataset announced via ProteomeXchange.

Title	Splice switching of SULT1C2 mRNA to lncRNA elicits tumor progression and immune evasion through triggering cholesterol biosynthesis
Description	Emerging evidence shows that protein-coding genes can produce noncoding splice forms in addition to their canonical mRNA transcripts. However, the coding-to-noncoding transformation of mRNA and its pathological significance in cancer remain poorly understood. Here, we explored the noncoding variants of protein-coding genes in hepatocellular carcinoma (HCC), and identified a novel sulfotransferase 1C2 (SULT1C2) noncoding variant, lncSULT1C2, as a driver of hepatic tumorigenesis. Polypyrimidine tract-binding protein 1 (PTBP1) mediates the splice switching of SULT1C2 pre-mRNA to lncSULT1C2. Increased lncSULT1C2 expression accelerated the tumorigenicity of HCC cells by reprogramming cholesterol biosynthesis. LncSULT1C2-induced cholesterol accumulation activated mTORC1 signaling and drove the PD-L1-mediated antitumor immune response. High lncSULT1C2 expression decreased the efficacy of anti-PD-1 immunotherapy in mice. GalNAc-conjugated antisense oligonucleotide (ASO) against lncSULT1C2 elicited robust antitumor effects. This study unravels lncSULT1C2 as a previously unrecognized oncogenic noncoding variant of SULT1C2 and highlight the relevance of lncSULT1C2 in cholesterol metabolism reprogramming and tumor immune evasion.
HostingRepository	iProX
AnnounceDate	2025-09-23
AnnouncementXML	Submission_2025-09-22_23:46:42.913.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Junjiao Song
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-22 23:46:15	ID requested
⏵ 1	2025-09-22 23:46:43	announced

Dataset with its publication pending

submitter keyword: SULT1C2, Splice switching, Cholesterol biosynthesis, Immune evasion

Xianghuo He
contact affiliation	Fudan University Shanghai Cancer Center
contact email	xhhe@fudan.edu.cn
lab head
Junjiao Song
contact affiliation	Fudan University Shanghai Cancer Center
contact email	junjiao_song@fudan.edu.cn
dataset submitter

iProX dataset URI