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

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

扫码查看
原文链接
  • 国家科技期刊平台
  • NETL
  • NSTL
  • 万方数据
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 mitogen-activated protein kinase(MAPK)pathway,promoted G2/M phase transition,and inhibited apoptosis in GC cells.Additionally,quercetin was identified as a selec-tive NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells,organoids,CDX,and PDX models.Conclusions:Collectively,NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression;addition-ally,NUF2 inhibitors exhibited potent anti-GC activity.This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

NUF2Gastric cancerQuercetinPatient-derived xenograftOrganoid

Bo Long、Huinian Zhou、Lixia Xiao、Xiangyan Jiang、Jian Li、Zhijian Ma、Na He、Wei Xin、Boya Zhang、Xiaoqin Zhu、Zeyuan Yu、Zuoyi Jiao

展开 >

The First Department of General Surgery,Lanzhou University Second Hospital,Lanzhou University,Lanzhou,Gansu 730000,China

Cuiying Biomedical Research Center,Lanzhou University Second Hospital,Lanzhou University,Lanzhou,Gansu 730000,China

The Second Clinical Medical School of Lanzhou University,Lanzhou University,Lanzhou,Gansu 730000,China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaMajor Project Granted by the Gansu Provincial Science and Technology DepartmentGansu Provincial Science and Technology Plan Project 21Cuiying Scientific and Technological Innovation Program of Lanzhou University Second HospitalGansu Province Science Foundation for YouthsCuiying Science and Technology Innovation Project of Lanzhou University Second HospitalCuiying Science and Technology Innovation Project of Lanzhou University Second HospitalCuiying Science and Technology Innovation Project of Lanzhou University Second HospitalCuiying Science and Technology Innovation Project of Lanzhou University Second Hospital

32170729821610062221ZD4FA015JR1RA144CY2020-MS1020JR5RA316CYXZ2020-10CY2020-MS10CYXZ2021-27CY2022-ZD-01

2024

10.1097/CM9.0000000000003006

中华医学杂志(英文版)
中华医学会

中华医学杂志(英文版)

CSTPCD
影响因子：0.838
ISSN：0366-6999
年,卷(期)：2024.137(20)