首页|SPATS2通过激活NOTCH信号通路促进喉鳞状细胞癌进展的机制研究

SPATS2通过激活NOTCH信号通路促进喉鳞状细胞癌进展的机制研究

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目的:探究丝氨酸精子发生相关蛋白2(spermatogenesis associated serine rich 2,SPATS2)影响喉 鳞 状 细 胞 癌(larynx squamous cell carcinoma,LSCC)增 殖、迁 移、侵 袭 和 上 皮 间 质 转 化(epithelial-mesenchymal transition,EMT)发生的分子机制,从而为寻找LSCC筛查、诊断和治疗的潜在靶点提供理论依据。方法:从TCGA数据库中下载LSCC临床及RNA-seq数据并进行整理,从中提取SPATS2的mRNA表达数据,并用R 4。3。1进行分析作图;用R4。3。1进行单基因差异分析后所得基因集进行基因本体分析(gene ontology,GO)和基因集富集分析(gene set enrichment analysis,GSEA);用CCK8、克隆形成实验、划痕实验、Transwell实验、Western blot验证敲减或过表达SPATS2后细胞的增殖、迁移和侵袭能力,用qRT-PCR检测目的基因mRNA水平变化,并用ImageJ、GraphPad Prism8和IBM SPSS Statistics 25对结果进行定量与统计学分析。结果:通过生信分析发现,LSCC组织中SPATS2的mRNA水平显著高于癌旁组织(P<0。001),且高水平SPATS2不利于患者生存(P=0。021)。过表达或敲减SPATS2后,细胞的增殖、迁移、侵袭能力及波形蛋白(Vimentin)、N-钙黏蛋白(N-Cadherin)、NOTCH1、cleaved-NOTCH1的表达水平、NOTCH信号通路下游靶基因的mRNA水平均随之升高或降低。在过表达SPATS2的同时抑制NOTCH信号通路可以逆转由单独过表达SPATS2导致的细胞增殖、迁移、侵袭能力增强和EMT水平升高的结果。结论:SPATS2能够通过影响NOTCH信号通路影响LSCC细胞的增殖、迁移、侵袭和EMT等恶性表型,进而影响LSCC进展。
SPATS2 promotes LSCC process by activating the NOTCH signaling pathway
Objective:This study aims to investigate the molecular mechanisms through which spermatogenesis associated ser-ine rich 2(SPATS2)influences larynx squamous cell carcinoma(LSCC)by affecting proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT).The findings will provide a theoretical basis for identifying potential targets for screen-ing,diagnosis,and treatment LSCC.Methods:Clinical and RNA-seq data for LSCC were obtained from the TCGA database and processed accordingly.SPATS2 mRNA expression data were extracted and analyzed using R 4.3.1 software.Gene ontology(GO)analysis and gene set enrichment analysis(GSEA)were conducted using the gene set obtained from single-gene differential analysis performed with R version 4.3.1.Proliferation,migration,and invasion abilities of cells were assessed through CCK8,col-ony formation,wound healing and Transwell assays.Western blotting was employed to assess protein expression,while qRT-PCR was used to measure mRNA levels of genes.Quantitative and statistical analyses were performed using ImageJ,Graph-Pad Prism 8,and IBM SPSS Statistics 25.Results:Bioinformatics analysis revealed significantly higher levels of SPATS2 mRNA in LSCC tissues compared to adjacent normal tissues(P<0.001),indicating an adverse impact on patient survival(P=0.021).Overexpression or knockdown of SPATS2 resulted in altered cell proliferation,migration,invasion,as well as changes in the expression levels of Vimentin,N-Cadherin,NOTCH1 and cleaved-NOTCH1,and downstream target genes of the NOTCH signaling pathway.Inducing overexpression of SPATS2 and inhibiting the NOTCH signaling pathway simultaneously could re-verse the enhanced cell proliferation,migration,invasion,and EMT caused by SPATS2 overexpression.Conclusion:SPATS2 exerts influence on the malignant characteristics of LSCC cells,including proliferation,migration,invasion,and EMT,by modu-lating the NOTCH signaling pathway,thus contributing to the progression of LSCC.

Larynx squamous cell carcinomaNOTCH signaling pathwaySPATS2ProliferationMetastasisEMT

张晓然、潘夏至、鲁钺皓、刘段莎丽、郑世康、王程、刘明波

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山东第二医科大学临床医学院,山东 潍坊 261000

解放军总医院海南医院耳鼻咽喉头颈外科,海南 三亚 572000

喉鳞状细胞癌 NOTCH信号通路 SPATS2 增殖 转移 上皮间质转化

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LCYX202105LCYX202202ZDKJ202005

2024

海南医学院学报
海南医学院

海南医学院学报

CSTPCD北大核心
影响因子:1.068
ISSN:1007-1237
年,卷(期):2024.30(18)
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