摘要
目的:探究口腔鳞癌(OSCC)细胞中BMI1调控肿瘤相关巨噬细胞(TAMs)表型转化的作用及其机制。方法:分析GEPIA 2.0网站中519例头颈鳞癌组织和44例正常组织中BMI1表达。实时荧光定量PCR、蛋白印迹法检测3例OSCC组织和SCC9、SCC15和CAL27细胞系中BMI1的表达;siRNA技术建立SCC9细胞的BMI1敲除细胞系,CCK-8、划痕实验、Transwell实验探究BMI1/NF-κB轴介导癌细胞恶性生物学行为;收集各组细胞条件培养基,通过OSCC细胞条件培养基与人单核细胞(THP-1)共培养,检测THP-1的募集和巨噬细胞分型相关标志物的表达情况。裸鼠荷瘤实验进一步体内检测BMI1对移植瘤增生的影响。结果:BMI1在OSCC组织以及细胞系中显著高表达;BMI1/NF-κB轴促进了OSCC细胞增殖、迁移和侵袭能力,也促进了THP-1细胞的募集与M2型极化。体内实验进一步证明了敲低BMI1可以抑制OSCC生长。结论:BMI1/NF-κB轴可通过调控TAMs的M2型转化,促进口腔鳞癌的增殖、迁移和侵袭能力。靶向阻断BMI1/NF-κB轴可能为口腔鳞癌治疗提供新靶点和新策略。
Objective:To investigate the impact of BMI1 expression in OSCC on the recruitment and differentiation of tumor-associated macrophages(TAMs).Methods:BMI1 expression in 519 cases of OSCC tissues and 44 normal controls was analyzed using online datasets of GEPIA 2.0,and validated in 3 cases of OSCC samples and controls by qRT-PCR and western blotting.The function of BMI1/NF-κB axis during OSCC carcinogenesis was investigated by CCK8 assays,wound healing test and transwell assays.Macrophage phenotypes and recruitment were determined using qRT-PCR and western blotting following coculture of the cells with human monocyte cells(THP-1)by OSCC conditioned medium.Moreover,a cell line-derived xenograft(CDX)model was used to detect the effect of BMI1 on tumor growth in vivo.Results:Compared with the normal tissues and cells,the expression level of BMI1 in OSCC tissues and cells was significantly upregulated.BMI1 knockdown impaired the proliferation,migration,and invasion abilities of OSCC cell lines in NF-κB-dependent manner.Furthermore,OSCC cells with high BMI1 expression inhibited the migration of THP-1 cells,promoted M2-like macrophage polarization through NF-κB pathway in vitro.Xenograft experiments further confirmed the inhibitory effect of BMI1 knockdown on the tumorigenesis ability of OSCC cells in vivo.Conclusion:BMI1 promotes M2-like polarization by regulating NF-κB and may be used as a potential therapeutic target for antitumor immunity.
作者
李雅慧
李欢
贺耀东
刘荣
黄军红
胡雅婷
李静
姚彦冰
杨新杰
魏建华
LI Yahui;LI Huan;HE Yaodong;LIU Rong;HUANG Junhong;HU Yating;LI Jing;YAO Yanbing;YANG Xinjie;WEI Jianhua(State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,National Clinical Research Center for Oral Diseases,Shaanxi Key Laboratory of Stomatology,Department of Oral and Maxillofacial Surgery,The Third Hospital Affiliated to Air Force Military Medical University,China,Xi'an 710032)
出处
《实用口腔医学杂志》
CAS
CSCD
北大核心
2024年第2期233-240,共8页
Journal of Practical Stomatology
基金
国家自然科学基金面上项目(编号:81973114)。
