海南医学院学报2024,Vol.30Issue(18):1370-1380,11.DOI:10.13210/j.cnki.jhmu.20240429.006
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 promotes LSCC process by activating the NOTCH signaling pathway
摘要
Abstract
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.关键词
喉鳞状细胞癌/NOTCH信号通路/SPATS2/增殖/转移/上皮间质转化Key words
Larynx squamous cell carcinoma/NOTCH signaling pathway/SPATS2/Proliferation/Metastasis/EMT分类
医药卫生引用本文复制引用
张晓然,潘夏至,鲁钺皓,刘段莎丽,郑世康,王程,刘明波..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[J].海南医学院学报,2024,30(18):1370-1380,11.基金项目
This study was supported by Molecular Typing Related Research on Laryngeal Cancer(LCYX202105),Pathogenic Mechanism of Laryngeal Cancer Based on Single Cell Sequencing and Spatial Transcriptome Technology(LCYX202202),Key Technology Research and Application of Cancer Prevention and Treatment in Hainan Province(ZDKJ202005) 喉癌的分子分型相关研究(LCYX202105),基于单细胞测序与空间转录组技术的喉癌致病机理研究(LCYX202202),海南省肿瘤防治关键技术研究与应用(ZDKJ202005) (LCYX202105)