Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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USP15 inhibits multiple myeloma cell apoptosis through activating a feedback loop with the transcription factor NF-κBp65

  • Zhou, Lili (Shanghai Jiahui International Hospital Cancer Center) ;
  • Jiang, Hua (Department of Hematology, Shanghai Changzheng Hospital, Second Military Medical University) ;
  • Du, Juan (Department of Hematology, Shanghai Changzheng Hospital, Second Military Medical University) ;
  • Li, Lu (Department of Hematology, Shanghai Changzheng Hospital, Second Military Medical University) ;
  • Li, Rong (Department of Hematology, Shanghai Changzheng Hospital, Second Military Medical University) ;
  • Lu, Jing (Department of Hematology, Shanghai Changzheng Hospital, Second Military Medical University) ;
  • Fu, Weijun (Department of Hematology, Shanghai Changzheng Hospital, Second Military Medical University) ;
  • Hou, Jian (Department of Hematology, Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine)
  • Received : 2018.05.16
  • Accepted : 2018.09.04
  • Published : 2018.11.30
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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-${\kappa}Bp65$, while USP15 overexpression exhibited an inverse effect. Moreover, in vivo experiments indicated that USP15 silencing inhibited MM tumor growth and NF-${\kappa}Bp65$ expression. PDTC treatment significantly inhibited USP15 overexpression-induced cell proliferation, apoptosis inhibition, and NF-${\kappa}Bp65$ expression. USP15 overexpression promoted NF-${\kappa}Bp65$ expression through inhibition of its ubiquitination, whereas NF-${\kappa}Bp65$ promoted USP15 expression as a positive regulator. Taken together, the USP15-NF-${\kappa}Bp65$ loop is involved in MM tumorigenesis and may be a potential therapeutic target for MM.

Keywords

Acknowledgement

Supported by : National Natural Science Foundation of China

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