title: PSMB4 promotes multiple myeloma cell growth by activating NF-κB-miR-21 signaling.
abstract: Proteasomal subunit PSMB4, was recently identified as potential cancer driver genes in several tumors. However, the regulatory mechanism of PSMB4 on carcinogenesis process remains unclear. In this study, we investigated the expression and roles of PSMB4 in multiple myeloma (MM). We found a significant up-regulation of PSMB4 in MM plasma and cell lines. Ectopic overexpression of PSMB4 promoted cell growth and colony forming ability of MM cells, whereas inhibition of PSMB4 led to a decrease of such events. Furthermore, our results demonstrated the up-regulation of miR-21 and a positive correlation between the levels of miR-21 and PSMB4 in MM. Re-expression of miR-21 markedly rescued PSMB4 knockdown-mediated suppression of cell proliferation and clone-formation. Additionally, while enforced expression of PSMB4 profoundly increased NF-κB activity and the level of miR-21, PSMB4 knockdown or NF-κB inhibition suppressed miR-21 expression in MM cells. Taken together, our results demonstrated that PSMB4 regulated MM cell growth in part by activating NF-κB-miR-21 signaling, which may represent promising targets for novel specific therapies.
authors: Department of Hematology, Navy General Hospital, Beijing 100048, China.
authors: Peihao
authors: P
authors: Zheng
authors: Department of Hematology, Navy General Hospital, Beijing 100048, China.
authors: Honggang
authors: H
authors: Guo
authors: School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006, China.
authors: Guangchao
authors: G
authors: Li
authors: Department of Medical Oncology, Jinling Hospital, Nanjing 210002, China.
authors: Siqi
authors: S
authors: Han
authors: Department of Stomatology, Jinling Hospital, Nanjing 210002, China.
authors: Fei
authors: F
authors: Luo
authors: Department of Hematology, Navy General Hospital, Beijing 100048, China. Electronic address: liuyi2033@163.com.
authors: Yi
authors: Y
authors: Liu
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C108898:PSMB4 protein, human; D046988:Proteasome Endopeptidase Complex
keywords: Multiple myeloma; NF-κB pathway; PSMB4; Proteasome; miR-21