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RNA-binding protein hnRNPU regulates multiple myeloma resistance to selinexor

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机构： [1]Department of Hematology, West China Hospital, Sichuan University, China [2]Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology China, China [3]Department of Hematology, The Affiliated Hospital of Chengdu University, China [4]School of Life Science, Sichuan University, China [5]Department of Hematology, Mian-yang Central Hospital, China

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关键词： Multiple myeloma hnRNPU Selinexor RNA-binding protein XPO1

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Multiple myeloma (MM) is an incurable haematological cancer. Selinexor is the first-in-class selective inhibitor of nuclear export (SINE) and was newly approved for the treatment of MM. Until now, very few studies have investigated selinexor resistance in MM. Heterogeneous nuclear ribonucleoprotein U (hnRNPU) is an RNA-binding protein and a component of hnRNP complexes. Here we found that hnRNPU regulates MM sensitivity to selinexor. Cell apoptosis assays were performed to compare selinexor-induced cell death in control knockdown (CTR-KD) and hnRNPU knockdown (hnR-KD) MM cells. HnRNPU knockdown-induced nuclear protein retention was examined by proteomics array. HnRNPU-conferred mRNA translation regulation was evaluated by sucrose gradient assay, RNA electrophoresis mobility shift assay, and RNA pull-down assay. We found that hnR-KD MM cells were more sensitive to selinexor-induced cell death in vitro and in mouse model. MM patients who responded to selinexor had relatively low hnRNPU expression. In brief, hnRNPU comprehensively regulated MM sensitivity to selinexor by affecting the localization of LTV1 and NMD3, and mRNA translation of MDM2 and RAN, which were involved in XPO1-mediated nuclear export of ribosome subunits and tumor suppressors. Our discoveries indicate that hnRNPU might be a possible marker to categorize MM patients for the use of Selinexor.Copyright © 2023. Published by Elsevier B.V.

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出版当年[2023]版：

大类 | 1 区

医学

小类 | 2 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 2 区肿瘤学

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第一作者机构： [1]Department of Hematology, West China Hospital, Sichuan University, China

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通讯机构： [1]Department of Hematology, West China Hospital, Sichuan University, China [2]Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology China, China [*1]Department of Hematology, West China Hospital, State Key Laboratory of Biotherapy and Cancer Center, Sichuan University. #37 Guo Xue Xiang Street, 610041, Chengdu, China. [*2]Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Dadao, Wuhan, 430022, China

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