Feifei Li, Ying Zhang, Jiahui Li, Ranran Jiang, Shusheng Ci
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引用次数: 0
Abstract
The nuclear pore complex (NPC) is an evolutionarily conserved structure that maintains the traffic between the nucleus and cytoplasm. Here, we profiled the expression of nucleoporins (NUPs) in glioblastoma stem cells (GSCs) and found that NUP98 promoted GSC maintenance and therapeutic resistance. GSCs preferentially expressed NUP98, which is essential for GSC tumorigenesis in vitro and in vivo. RNA sequencing demonstrated that NUP98 regulated the expression of key DNA damage and repair pathways. NUP98 formed a complex with transcription factor p65 to directly activate genes involved in homologous repair. Attenuation of NUP98 or p65 expression induced unrepaired intrinsic DNA damage and sensitized GSC to ionizing radiation. Clinically, overexpression of NUP98 informs poor clinical outcome among glioblastoma (GBM) patients. Collectively, our results demonstrate that NUP98-p65 represents a novel node in the regulation of DNA repair, suggesting a therapeutic strategy with potential clinical benefits for GBM patients.
期刊介绍：
The FASEB Journal publishes international, transdisciplinary research covering all fields of biology at every level of organization: atomic, molecular, cell, tissue, organ, organismic and population. While the journal strives to include research that cuts across the biological sciences, it also considers submissions that lie within one field, but may have implications for other fields as well. The journal seeks to publish basic and translational research, but also welcomes reports of pre-clinical and early clinical research. In addition to research, review, and hypothesis submissions, The FASEB Journal also seeks perspectives, commentaries, book reviews, and similar content related to the life sciences in its Up Front section.
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