PXD059712

PXD059712 is an original dataset announced via ProteomeXchange.

Title	lnc-FAM72D-3 augments the affinity of the E3 ubiquitin ligase HECTD3 for MBNL1, inciting lysine 48-linked ubiquitination and subsequent degradation of MBNL1
Description	Lenvatinib resistance (LR) profoundly exacerbates the prognosis of patients afflicted with advanced hepatocellular carcinoma (HCC). As pivotal mediators of intercellular communication, exosomes have been implicated in the development of LR. Nonetheless, the precise contributions of exosome-derived long non-coding RNAs (lncRNAs) to this phenomenon remain inadequately elucidated. Our prior investigations identified that lnc-FAM72D-3 is markedly up-regulated in the serum exosomes of HCC patients, yet its specific functions and underlying mechanisms remain only partially defined. In this study, we established lenvatinib-resistant HCC cell lines and organoids and demonstrated, through rigorous in vitro and in vivo experiments, that exosome-derived lnc-FAM72D-3 facilitates HCC progression and contributes to the phenomenon of LR. Mechanistically, lnc-FAM72D-3 augments the affinity of the E3 ubiquitin ligase HECTD3 for MBNL1, inciting lysine 48-linked ubiquitination and subsequent degradation of MBNL1. This degradation diminishes the interaction between MBNL1 and focal adhesion kinase (FAK), precipitating the de-nucleation of FAK and its activation by phosphorylation. The activated FAK subsequently reorganizes the cytoskeleton, markedly enhancing the proliferation, invasion, and stemness of HCC cells, thereby fostering LR. In summary, this investigation offers novel mechanistic insights into the regulatory role of exosomal lncRNAs in LR and posits a potential therapeutic strategy aimed at mitigating LR in patients with HCC.
HostingRepository	iProX
AnnounceDate	2025-01-10
AnnouncementXML	Submission_2025-01-12_22:57:14.623.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mingbo Cao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-12 22:56:54	ID requested
⏵ 1	2025-01-12 22:57:15	announced

Dataset with its publication pending

submitter keyword: Hepatocellular Carcinoma, LR, Long non-coding RNAs, Cytoskeleton remodeling

Zhicheng Yao
contact affiliation	The Third Affiliated Hospital, Sun Yat-sen University
contact email	yaozhch2@mail.sysu.edu.cn
lab head
Mingbo Cao
contact affiliation	The Third Affiliated Hospital, Sun Yat-sen University
contact email	15521399326@163.com
dataset submitter

iProX dataset URI