PXD024557

PXD024557 is an original dataset announced via ProteomeXchange.

Title	Evolvement of Chromosomal instability in drug-resistance by BUB1B and circBUB1B_544aa in multiple myeloma
Description	Multiple myeloma (MM) is still an incurable plasma cell malignancy with heterogeneity characterized by drug resistance and disease recurrence. Chromosome instability (CIN), served as the hallmark of cancers, is a key component of drug resistance, the acquisition of tumor heterogeneity, tumor progression and relapse, whereas the function of the CIN in cancer, especially its coordination with MM, is not clear. In this study, we elucidated that the expression of BUB1 beta (BUB1B) was elevated strikingly in MM patients and its high expression has been implicated in dictating malignant progression. Overexpression of BUB1B facilitated cellular proliferation and induced drug resistance in vitro and in a xenograft myeloma mouse model, while genetic targeting BUB1B abrogated this effect. Mechanistic studies unveiled that enforced expression of BUB1B evoked CIN to favor MM progression mainly through phosphorylating CEP170. Intriguingly, we discovered circBUB1B_544aa, which encoded by a circular RNA circBUB1B and contained BUB1B kinase catalytic center, played a synergistic role with BUB1B in evoking CIN through CEP170 activation. Besides, MM cells could secrete circBUB1B_544aa in MM microenvironment to interfere adjacent or distant cells. Thus, enzymatic catalytic center encoded by BUB1B and circBUB1B_544aa represents a strong predictor for drug-resistance and poor prognosis, which would shed light on the mechanisms underlying drug resistance and relapse in MM. Finally, siRNA targeting the common sequence of BUB1B and circBUB1B_544aa could significantly inhibit MM growth both in vitro and in vivo indicating that BUB1B is a promising and potential therapeutic target of MM.
HostingRepository	iProX
AnnounceDate	2021-03-04
AnnouncementXML	Submission_2021-03-06_19:45:42.704.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaozhu Tang
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	2021-03-06 19:42:18	ID requested
⏵ 1	2021-03-06 19:45:43	announced

Dataset with its publication pending

submitter keyword: multiple myeloma, BUB1B, circBUB1B_544aa, proliferation, drug resistance, chromosomal instability

Ye Yang
contact affiliation	Nanjing University of Chinese Medicine
contact email	yangye876@sina.com
lab head
Xiaozhu Tang
contact affiliation	Nanjing University of Chinese Medicine
contact email	tangxz1130@163.com
dataset submitter

iProX dataset URI