PXD063781

PXD063781 is an original dataset announced via ProteomeXchange.

Title	TRMU Confers Resistance of Melanoma Cells to Vemurafenib through Modulating Mitochondrial Electron Transport Chain Activities
Description	Melanoma is the fifth most common newly diagnosed cancer in the U.S., where substitution of valine 600 with glutamic acid (V600E) in BRAF is the most frequently observed mutation in melanoma. Vemurafenib is an FDA-approved kinase inhibitor for BRAFV600E; while the drug can elicit effective remission of metastatic melanoma, relapse typically occurs within several months after treatment. Recent studies documented critical roles of reversible modifications of RNA in modulating resistance to cancer therapy. In the present study, we aim to explore the contributions of epitranscriptomic alterations to vemurafenib resistance by assessing the differential expression of epitranscriptomic reader, writer and eraser (RWE) proteins in IGR37 metastatic melanoma cells and the isogenic vemurafenib-resistant cells (IGR37xp). Our results revealed altered expressions of multiple epitranscriptomic RWE proteins, including markedly elevated expressions of MTO1 and TRMU – which act sequentially to produce 5-taurinomethyl-2-thiouridine (τm5s2U) at the 34th position of human mitochondrial (mt) tRNAGlu, tRNAGln and tRNALys – in the resistant line. We found that genetic depletion of TRMU re-sensitizes IGR37xp cells to vemurafenib and reduces mitochondrion respiration. Interestingly, oxidative phosphorylation proteins exhibit attenuated expression in IGR37xp than IGR37 cells and also in TRMU-knockdown IGR37xp cells. Together, we reported, for the first time, the role of an mt tRNA-modifying enzyme in conferring vemurafenib resistance in melanoma.
HostingRepository	PRIDE
AnnounceDate	2025-12-08
AnnouncementXML	Submission_2025-12-07_16:14:23.517.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Shiyuan Guo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-05-08 19:07:27	ID requested
⏵ 1	2025-12-07 16:14:24	announced

10.1021/acs.jproteome.5c00805;

Guo S, Qi T, Wang Y, TRMU Confers Resistance of Melanoma Cells to Vemurafenib through Modulating Mitochondrial Activities. J Proteome Res, 24(12):5913-5920(2025) [pubmed]

submitter keyword: vemurafenib resistance, mitochondrion,melanoma

Yinsheng Wang
contact affiliation	University of California Riverside
contact email	yinsheng@ucr.edu
lab head
Shiyuan Guo
contact affiliation	Genetics, Genomics and Bioinformatics Graduate Program, University of California, Riverside
contact email	sguo039@ucr.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD063781
     1. Label: PRIDE project
     2. Name: TRMU Confers Resistance of Melanoma Cells to Vemurafenib through Modulating Mitochondrial Electron Transport Chain Activities