敲低HMGN2可抑制肺腺癌细胞的增殖、迁移和侵袭  

Knocking down HMGN2 can inhibit the proliferation,migration,and invasion of lung adenocarcinoma cells

作　　者：陈直 朱潇 杏福宝 宋超 耿阳 王伟 张雷 Chen Zhi;Zhu Xiao;Xing Fubao;Song Chao;Geng Yang;Wang Wei;Zhang Lei(Anhui Provincial Key Laboratory of Cancer Translational Medicine,Bengbu Medical University,Bengbu 233000;Dept of Thoracic Surgery,The First Affiliated Hospital of Bengbu Medical University,Bengbu 233000)

机构地区：[1]蚌埠医科大学癌症转化医学安徽省重点实验室,蚌埠233000 [2]蚌埠医科大学第一附属医院胸外科,蚌埠233000

出　　处：《安徽医科大学学报》2025年第3期472-479,487,共9页Acta Universitatis Medicinalis Anhui

基　　金：安徽省高校自然科学研究项目(编号:2023AH052005);蚌埠医学院科技项目自然科学类(编号:2022byzd066)。

摘　　要：目的探究高迁移率蛋白N2(HMGN2)对肺腺癌细胞的影响及作用机制。方法通过TCGA数据库分析HMGN2与肺腺癌组织之间的关联。收集肺腺癌组织及其相邻正常组织,比较HMGN2的表达水平差异。利用定量逆转录聚合酶链反应(qRT-PCR)、Western blot,检测肺腺癌细胞株A549和NC-H1299中HMGN2 mRNA的表达情况。通过si-RNA技术敲低HMGN2表达,分为对照组(转染同剂量NC-siRNA片段)和si-RNA组。根据si-RNA敲低效率,构建稳定转染的细胞株。采用CCK-8、Transwell实验、划痕实验、单克隆形成实验以及EdU实验等方法,评估HMGN2敲低后对肺腺癌细胞增殖、迁移和侵袭能力的影响。转录组测序分析揭示HMGN2与肿瘤发生的相关通路。Western blot检测敲低HMGN2后,MAPK通路蛋白的相对表达情况。结果HMGN2的mRNA在肺癌组织和肺腺癌细胞株中表达量明显升高(P<0.05)。抑制HMGN2表达后,细胞增殖、迁移和侵袭等功能显著下降(P<0.05),MAPK信号通路的磷酸化水平明显降低(P<0.05)。结论HMGN2在肺腺癌细胞中具有促进增殖、迁移、侵袭的作用,其机制可能与MAPK通路的磷酸化激活水平密切相关。Objective To investigate the effects and underlying mechanisms of high mobility group nucleosome-binding domain protein 2(HMGN2)on lung adenocarcinoma cells.Methods This work first analyzed the association between HMGN2 and lung adenocarcinoma tissues using The Cancer Genome Atlas(TCGA)database.Lung adenocarcinoma tissues and adjacent normal tissues were collected to compare the differential expression levels of HMGN2.The expression of HMGN2 mRNA in lung adenocarcinoma cell lines A549 and NC-H1299 were detected by qRT-PCR and Western blot.HMGN2 expression was knocked down using si-RNA technology,with the control group transfected with an equivalent amount of NC-siRNA,and the si-RNA group transfected with si-HMGN2.Stable transfected cell lines were established based on si-RNA knockdown efficiency.The effects of HMGN2 knockdown on the growth,movement,and spread of lung adenocarcinoma cells were assessed using CCK-8,Transwell assays,scratch assays,colony formation assays,and EdU assays.Transcriptome sequencing analysis revealed pathways related to tumorigenesis associated with HMGN2.The relative expression levels of MAPK pathway proteins after HMGN2 knockdown were detected by Western blot.Results HMGN2 mRNA expression was significantly elevated in lung cancer tissues and lung adenocarcinoma cell lines(P<0.05).After HMGN2 knockdown,cell proliferation,migration,and invasion were significantly reduced(P<0.05),and the phosphorylation levels of the MAPK signaling pathway markedly decreased(P<0.05).Conclusion HMGN2 enhances the proliferation,migration,and invasion of lung adenocarcinoma cells,and its mechanism may be closely related to the activation of the MAPK signaling pathway via phosphorylation.

关 键 词：肺腺癌 HMGN2 增殖 迁移 侵袭 MAPK信号通路 

分 类 号：R734.2[医药卫生—肿瘤]