PXD051634

PXD051634 is an original dataset announced via ProteomeXchange.

Title	Inhibition of FBP1 expression by KMT5A through TWIST1 methylation is one of the mechanisms leading to chemoresistance in breast cancer
Description	Lysine methyltransferase 5A (KMT5A) is the sole mammalian enzyme known to catalyze the monomethylation of histone H4 lysine 20 (H4K20mel) and nonhistone proteins such as p53, which are involved in the occurrence and progression of many cancers. Our study aimed to determine the function of KMT5A in inducing docetaxel resistance in patients with breast carcinoma by evaluating glucose metabolism and the underlying mechanism involved. KMT5A is highly expressed in breast cancer cells; therefore, we examined the upregulation or downregulation of KMT5A-related proteins after KMT5A knockdown in breast cancer cells by TMT proteomics. Through differential protein expression and pathway enrichment analysis, the upregulated key gluconeogenic enzyme fructose-1,6-bisphosphatase 1 (FBP1) was found. Loss of FBP1 expression is closely related to the development and prognosis of various tumors. A dual-luciferase reporter gene assay confirmed that KMT5A inhibited the expression of FBP1 and that overexpression of FBP1 could enhance the chemotherapeutic sensitivity to docetaxel through the suppression of KMT5A expression. The KMT5A inhibitor UNC0379 was used to verify that docetaxel resistance induced by KMT5A through the inhibition of FBP1 depended on the methylase activity of KMT5A. According to previous literature reports and the database interaction network structure, we found that KMT5A acts on the transcription factor TWIST1. Then, we verified that TWSIT1 promoted the expression of FBP1 by using dual-luciferase reporter gene experiments. Depending on its methylase activity, KMT5A can positively regulate glycolysis-mediated chemotherapy resistance by inhibiting the transcription of FBP1 in collaboration with TWIST1. KMT5A affects chemotherapy resistance by regulating the cell cycle, which represents another potential therapeutic target for KMT5A.
HostingRepository	iProX
AnnounceDate	2024-04-20
AnnouncementXML	Submission_2024-06-05_22:05:50.551.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xue Peng
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	TMT6plex reporter fragment
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-22 00:13:30	ID requested
⏵ 1	2024-06-05 22:05:50	announced

Dataset with its publication pending

submitter keyword: KMT5A, glucose metabolism, chemoresistance,breast cancer,FBP1

Xue Peng
contact affiliation	Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
contact email	2056592642@qq.com
lab head
Xue Peng
contact affiliation	Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
contact email	2056592642@qq.com
dataset submitter

iProX dataset URI