Targeting NUF2 suppresses gastric cancer progression through G2/M phase arrest and apoptosis induction

作者：Bo Long, Huinian Zhou, Lixia Xiao, Xiangyan Jiang, Jian Li, Zhijian Ma, Na He, Xin Wei, Boya Zhang, Xiaoqin Zhu, Zeyuan Yu, Zuoyi Jiao · 发表于：Chinese Medical Journal · 年份：2024 · DOI：10.1097/cm9.0000000000003006 · 被引用次数：10 · 研究领域：Microtubule and mitosis dynamics、RNA Research and Splicing、Hippo pathway signaling and YAP/TAZ

BACKGROUND: Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2 , a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. METHODS: Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2 -associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. RESULTS: NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro . NUF2 significantly regulated the ...