Inhibition of USP1 induces apoptosis via ID1/AKT pathway in B-cell acute lymphoblastic leukemia cells

Autor: Weili Wang, Zhaoyuan Zhang, Xingyi Kuang, Tingting Lu, Jie Xiong, Jishi Wang
Rok vydání: 2020
Předmět:
Adult
Inhibitor of Differentiation Protein 1
Male
Adolescent
Cellular differentiation
SJB3-019A
Down-Regulation
Apoptosis
B-cell acute lymphoblastic leukemia
03 medical and health sciences
Young Adult
0302 clinical medicine
Downregulation and upregulation
Bone Marrow
Cell Line
Tumor
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
medicine
Humans
RNA
Small Interfering
Child
PI3K/AKT/mTOR pathway
Cell Proliferation
Gene knockdown
Akt/PKB signaling pathway
Cell growth
Chemistry
Gene Expression Regulation
Leukemic
ID1
General Medicine
PI3K/AKT pathway
USP1
medicine.anatomical_structure
Gene Knockdown Techniques
Cancer research
Disease Progression
030211 gastroenterology & hepatology
Female
Bone marrow
Ubiquitin-Specific Proteases
Protein Processing
Post-Translational
Proto-Oncogene Proteins c-akt
Research Paper
Signal Transduction
Zdroj: International Journal of Medical Sciences
ISSN: 1449-1907
Popis: Deubiquitylating enzyme ubiquitin-specific protease 1 (USP1) has been reported to be aberrantly overexpressed in cancers, and it plays a critical role in regulating various cellular processes, such as cell proliferation, apoptosis, and cell differentiation. However, the role of USP1 in B-cell acute lymphoblastic leukemia (B-ALL) remains largely undefined. USP1 expression in 30 newly diagnosed B-ALL patients was detected by real-time PCR and western blot. We found that USP1 was generally upregulated in the bone marrow cells derived from B-ALL patients. Knockdown of USP1 by siRNA decreased B-ALL cell growth and induced apoptosis. Similarly, pharmacological inhibition of USP1 by SJB3-019A significantly repressed cell proliferation and triggered B-ALL cell apoptosis. Finally, we found that inhibition of USP1 downregulated the expression of ID1 and p-AKT, and upregulated ID1 expression could reverse the suppressive effects of USP1 inhibitor in B-ALL cells. Taken together, these results demonstrate that USP1 promote B-ALL progression at least partially via the ID1/AKT signaling pathway, and USP1 inhibitors might be promising therapeutic application for B-ALL.
Databáze: OpenAIRE
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