胃癌（GC）是一种预后不良的恶性肿瘤，是全球癌症相关死亡的主要原因之一；因此，确定新的治疗靶点对其相应的治疗至关重要。 NUF2 是 NDC80 着丝粒复合体的一个组成部分，可促进多种恶性肿瘤的癌症进展。因此，本研究旨在探讨NUF2作为抑制GC进展的治疗靶点的潜力。 2016年至2021年兰州大学第二医院接受GC根治性切除术的患者的临床样本、细胞计数测定、集落形成测定和细胞使用衍生的异种移植（CDX）模型来确定NUF2对GC进展的影响。采用流式细胞术检测NUF2或槲皮素对细胞周期进程和凋亡的影响。进行活细胞延时成像测定以确定 NUF2 对有丝分裂进展调节的影响。转录组学用于研究 NUF2 相关的分子机制。使用虚拟对接和微尺度热泳来鉴定 NUF2 抑制剂。最后，利用CDX、类器官和患者来源的异种移植（PDX）模型来检验NUF2抑制剂在GC中的疗效。NUF2表达在GC中显着增加，并且与预后呈负相关。 NUF2 的缺失在体内和体外均抑制了 GC 进展。 NUF2显着调节丝裂原激活蛋白激酶（MAPK）通路，促进G2/M期转变，并抑制GC细胞的凋亡。此外，槲皮素被确定为一种低毒性的选择性NUF2抑制剂，可显着抑制GC细胞、类器官、CDX和PDX模型中的肿瘤生长。总的来说，NUF2介导的G2/M期转变和凋亡抑制促进了GC进展；此外，NUF2 抑制剂表现出有效的抗 GC 活性。这项研究提供了一种在临床环境中靶向 NUF2 抑制 GC 进展的新策略。版权所有 © 2024 中华医学会，由 Wolters Kluwer, Inc. 根据 CC-BY-NC-ND 许可制作。

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.Clinical samples 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.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 mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models.Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.