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https://doi.org/10.1038/ncomms10258
| Title: | The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival | Authors: | Ohguchi, H Hideshima, T Bhasin, M.K Gorgun, G.T Santo, L Cea, M Samur, M.K Mimura, N Suzuki, R Tai, Y.-T Carrasco, R.D Raje, N Richardson, P.G Munshi, N.C Harigae, H Sanda, T Sakai, J Anderson, K.C |
Keywords: | caspase 7 caspase 8 histone demethylase histone H3 interferon regulatory factor 4 kruppel like factor 2 nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase protein KDM3A unclassified drug histone histone demethylase interferon regulatory factor interferon regulatory factor-4 KDM3A protein, human KLF2 protein, human kruppel like factor anatomy apoptosis bone cells and cell components gene expression tumor animal cell animal experiment animal model animal tissue apoptosis Article autoregulation bone marrow bone marrow stroma cell cell adhesion cell homing cell interaction cell survival controlled study gene silencing histone demethylation human human cell immunoblotting in vitro study in vivo study male microarray analysis monoclonal immunoglobulinemia mouse multiple myeloma myeloma cell nonhuman transactivation upregulation cell motion gene expression regulation genetics metabolism physiology tumor cell line Cell Adhesion Cell Line, Tumor Cell Movement Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Histones Humans Interferon Regulatory Factors Jumonji Domain-Containing Histone Demethylases Kruppel-Like Transcription Factors Multiple Myeloma |
Issue Date: | 2016 | Publisher: | Nature Publishing Group | Citation: | Ohguchi, H, Hideshima, T, Bhasin, M.K, Gorgun, G.T, Santo, L, Cea, M, Samur, M.K, Mimura, N, Suzuki, R, Tai, Y.-T, Carrasco, R.D, Raje, N, Richardson, P.G, Munshi, N.C, Harigae, H, Sanda, T, Sakai, J, Anderson, K.C (2016). The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival. Nature Communications 7 : 10258. ScholarBank@NUS Repository. https://doi.org/10.1038/ncomms10258 | Rights: | Attribution 4.0 International | Abstract: | KDM3A is implicated in tumorigenesis; however, its biological role in multiple myeloma (MM) has not been elucidated. Here we identify KDM3A-KLF2-IRF4 axis dependence in MM. Knockdown of KDM3A is toxic to MM cells in vitro and in vivo. KDM3A maintains expression of KLF2 and IRF4 through H3K9 demethylation, and knockdown of KLF2 triggers apoptosis. Moreover, KLF2 directly activates IRF4 and IRF4 reciprocally upregulates KLF2, forming a positive autoregulatory circuit. The interaction of MM cells with bone marrow milieu mediates survival of MM cells. Importantly, silencing of KDM3A, KLF2 or IRF4 both decreases MM cell adhesion to bone marrow stromal cells and reduces MM cell homing to the bone marrow, in association with decreased ITGB7 expression in MAF-translocated MM cell lines. Our results indicate that the KDM3A-KLF2-IRF4 pathway plays an essential role in MM cell survival and homing to the bone marrow, and therefore represents a therapeutic target. © 2016, Nature Publishing Group. All rights reserved. | Source Title: | Nature Communications | URI: | https://scholarbank.nus.edu.sg/handle/10635/182516 | ISSN: | 2041-1723 | DOI: | 10.1038/ncomms10258 | Rights: | Attribution 4.0 International |
| Appears in Collections: | Elements Staff Publications |
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