KMID : 0620920180500110151
|
|
Experimental & Molecular Medicine 2018 Volume.50 No. 11 p.151 ~ p.151
|
|
USP15 inhibits multiple myeloma cell apoptosis through activating a feedback loop with the transcription factor NF-¥êBp65
|
|
Zhou Lili
Jiang Hua Du Juan Li Lu Li Rong Lu Jing Fu Weijun Hou Jian
|
|
Abstract
|
|
|
USP15 has been shown to stabilize transcription factors, to be amplified in many cancers and to mediate cancer cell survival. However, the underlying mechanism by which USP15 regulates multiple myeloma (MM) cell proliferation and apoptosis has not been established. Here, our results showed that USP15 mRNA expression was upregulated in MM patients. USP15 silencing induced MM cell proliferation inhibition, apoptosis, and the expression of nuclear and cytoplasmic NF-¥êBp65, while USP15 overexpression exhibited an inverse effect. Moreover, in vivo experiments indicated that USP15 silencing inhibited MM tumor growth and NF-¥êBp65 expression. PDTC treatment significantly inhibited USP15 overexpression-induced cell proliferation, apoptosis inhibition, and NF-¥êBp65 expression. USP15 overexpression promoted NF-¥êBp65 expression through inhibition of its ubiquitination, whereas NF-¥êBp65 promoted USP15 expression as a positive regulator. Taken together, the USP15-NF-¥êBp65 loop is involved in MM tumorigenesis and may be a potential therapeutic target for MM.
|
|
KEYWORD
|
|
Targeted therapies, Ubiquitylation
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|