Stabilization of KPNB1 by deubiquitinase USP7 promotes glioblastoma progression through the YBX1-NLGN3 axis

作者：Jie Li, Bin Zhang, Zishan Feng, Dandan An, Zhiyuan Zhou, Chao Wan, Yan Hu, Yajie Sun, Yijun Wang, Xixi Liu, Wenwen Wei, Xiao Yang, Jingshu Meng, Mengjie Che, Yuhan Sheng, Bian Wu, Lu Wen, Fang Huang, Yan Li, Kunyu Yang · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2024 · DOI：10.1186/s13046-024-02954-8 · 被引用次数：19 · 研究领域：Nuclear Structure and Function、Ubiquitin and proteasome pathways、Microtubule and mitosis dynamics

BACKGROUND: Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. It is an aggressive tumor characterized by rapid proliferation, diffuse tumor morphology, and poor prognosis. Unfortunately, current treatments, such as surgery, radiotherapy, and chemotherapy, are unable to achieve good outcomes. Therefore, there is an urgent need to explore new treatment targets. A detailed mechanistic exploration of the role of the nuclear pore transporter KPNB1 in GBM is lacking. This study demonstrated that KPNB1 regulated GBM progression through a transcription factor YBX1 to promote the expression of post-protrusion membrane protein NLGN3. This regulation was mediated by the deubiquitinating enzyme USP7. METHODS: A tissue microarray was used to measure the expression of KPNB1 and USP7 in glioma tissues. The effects of KPNB1 knockdown on the tumorigenic properties of glioma cells were characterized by colony formation assays, Transwell migration assay, EdU proliferation assays, CCK-8 viability assays, and apoptosis analysis using flow cytometry. Transcriptome sequencing identified NLGN3 as a downstream molecule that is regulated by KPNB1. Mass spectrometry and immunoprecipitation were performed to analyze the potential interaction between KPNB1 and YBX1. Moreover, the nuclear translocation of YBX1 was determined with nuclear-cytoplasmic fractionation and immunofluorescence staining, and chromatin immunoprecipitation assays were conducted to study DNA binding...