title: SENP1 inhibition induces apoptosis and growth arrest of multiple myeloma cells through modulation of NF-κB signaling.
abstract: SUMO/sentrin specific protease 1 (Senp1) is an important regulation protease in the protein sumoylation, which affects the cell cycle, proliferation and differentiation. The role of Senp1 mediated protein desumoylation in pathophysiological progression of multiple myeloma is unknown. In this study, we demonstrated that Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. Lentivirus-mediated Senp1 knockdown triggers apoptosis and reduces viability, proliferation and colony forming ability of MM cells. The NF-κB family members including P65 and inhibitor protein IkBα play important roles in regulation of MM cell survival and proliferation. We further demonstrated that Senp1 inhibition decreased IL-6-induced P65 and IkBα phosphorylation, leading to inactivation of NF-кB signaling in MM cells. These results delineate a key role for Senp1in IL-6 induced proliferation and survival of MM cells, suggesting it may be a potential new therapeutic target in MM.
authors: Graduate School of Anhui Medical University, Hefei, PR China; Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors: Jun
authors: J
authors: Xu
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors: Hui-Yan
authors: HY
authors: Sun
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors: Feng-Jun
authors: FJ
authors: Xiao
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors: Hua
authors: H
authors: Wang
authors: Department of Hematology, General Hospital of Air Force, Beijing, PR China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Hematology, PLA General Hospital, Beijing, PR China.
authors: Lu
authors: L
authors: Wang
authors: Department of Hematology, PLA General Hospital, Beijing, PR China.
authors: Chun-Ji
authors: CJ
authors: Gao
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors: Zi-Kuan
authors: ZK
authors: Guo
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, PR China.
authors: Chu-Tse
authors: CT
authors: Wu
authors: Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China; Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, PR China. Electronic address: Wangls@bmi.ac.cn.
authors: Li-Sheng
authors: LS
authors: Wang
mesh_terms: D017209:Apoptosis; D002455:Cell Division; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D057809:HEK293 Cells; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases
keywords: IL-6; Multiple myeloma; NF-кB; Senp1