PXD066129

PXD066129 is an original dataset announced via ProteomeXchange.

Title	A micropeptide encoded by DSP-AS1 promotes lung adenocarcinoma by facilitating YTHDF1-induced oncogene translation initiation
Description	Functional micropeptides embedded within RNA transcripts previously classified as noncoding may play significant roles in lung tumorigenesis that remain largely unexplored. By integrating ribosome sequencing and mass spectrometry data, we identified a 46-amino-acid oncogenic micropeptide encoded by the lncRNA DSP-AS1, which we have named Translation Initiation Activated Micropeptide (TIAMP), in lung adenocarcinoma (LUAD). TIAMP is aberrantly overexpressed in LUAD and is associated with poor prognosis. Its oncogenic effects—including enhanced proliferation, survival, and invasiveness—were confirmed in both in vitro and in vivo models. TIAMP colocalizes with the translation machinery and orchestrates translational reprogramming by selectively promoting the translation of mRNAs encoding oncogenic factors in LUAD. Mechanistically, TIAMP binds to both eIF4G, a cap-binding subunit, and YTHDF1, an m6A reader that recruits eIF3 to methylated mRNAs, thereby forming a "closed loop" between YTHDF1 and eIF4G. This interaction positions YTHDF1 in proximity to the translation initiation complex, facilitating the efficient loading of the 40S ribosomal subunit onto target mRNAs. Targeting TIAMP yields significant anticancer effects both in vitro and in vivo. Our findings uncover the oncogenic role of this previously uncharacterized micropeptide in orchestrating mRNA translation, providing a compelling rationale for the development of anti-LUAD therapies targeting the translation machinery.
HostingRepository	iProX
AnnounceDate	2025-07-11
AnnouncementXML	Submission_2025-07-14_19:22:01.585.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zhenchuan Liu
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	2025-07-14 19:21:46	ID requested
⏵ 1	2025-07-14 19:22:01	announced

Dataset with its publication pending

submitter keyword: YTHDF1, IP-MS

Yongxin Zhou
contact affiliation	Shanghai Tongji Hospital Affiliated with Tongji University
contact email	zhou6302@tongji.edu.cn
lab head
Zhenchuan Liu
contact affiliation	Tongji University
contact email	liuzhenchuan1991@hotmail.com
dataset submitter

iProX dataset URI