血管抑制蛋白2在三阴性乳腺癌中的功能及其调控可变剪接机制  

Function of vasohibin-2 and the mechanism of alternative splicing in triple-negative breast cancer

作　　者：王卫 王红丽[1] 阿力比亚提·艾尼[1] 衣力亚尔·肉苏 阿依努尔[1] 杨亮[1] WANG Wei;WANG Hongli;ALIBIYATI·Aini;YILIYAER·Rousu;AYINUER;YANG Liang(Department of Head and Neck Surgery,Xinjiang Medical University Affiliated Cancer Hospital,Urumqi 830011,China)

机构地区：[1]新疆医科大学附属肿瘤医院头颈外科,乌鲁木齐830011

出　　处：《上海交通大学学报(医学版)》2024年第12期1526-1535,共10页Journal of Shanghai Jiao tong University:Medical Science

基　　金：新疆维吾尔自治区自然科学基金项目(2020D01C211)。

摘　　要：目的·探索血管抑制蛋白2(vasohibin-2,VASH2)在三阴性乳腺癌(triple-negative breast cancer,TNBC)中的表达及VASH2通过调控基因表达和可变剪接在TNBC发生发展中的作用机制。方法·通过基因型-组织表达数据库(GenotypeTissue Expression,GTEx)联合癌症基因组图谱数据库(The Cancer Genome Atlas,TCGA)比较VASH2在TNBC中与正常乳腺组织中的表达差异,并分析VASH2在TNBC中的甲基化水平。在TNBC细胞系MDA-MB-231中对VASH2过表达,并进行转录组测序,分析受VASH2所调控的差异表达基因及可变剪接基因。结果·VASH2在TNBC组织中与正常组织及其他乳腺癌分型比较表达水平显著提高。VASH2基因的低甲基化可能是VASH2在TNBC中表达上调的原因之一。VASH2过表达后引起81个基因显著差异表达,其中上调的基因23个,下调的基因58个。VASH2过表达后可变剪接水平发生显著变化的基因主要富集在细胞周期、p53信号通路上。结论·VASH2可能通过调控TNBC中基因可变剪接促进其发生和发展。Objective·To explore the role of vasohibin-2(VASH2)in the regulation of proliferation and metastasis of triplenegative breast cancer(TNBC)cells,and explore the mechanism of VASH2 in the occurrence and development of TNBC through regulation of gene expression and alternative splicing.Methods·TCGA-GTEx was used to analyze the expression of VASH2 in TNBC.VASH2 methylation levels in TNBC were also analyzed.VASH2 was overexpressed in the MDA-MB-231 human TNBC cell line and transcriptome sequencing was performed.Differentially expressed genes and alternatively spliced genes regulated by VASH2 were analyzed to explore the mechanism of action of VASH2 in TNBC.Results·VASH2 was significantly overexpressed in TNBC compared to the normal tissues.Hypomethylation of the VASH2 gene was implicated in the upregulation of VASH2 expression in TNBC.Overexpression of VASH2 caused significant differential expression of 81 genes,of which 23 genes were upregulated and 58 genes were down-regulated.Genes with significantly altered alternative splicing levels due to VASH2 overexpressed were enriched in cell cycle and p53 signaling pathways.Conclusion·VASH2 regulates the alternative splicing of TNBC oncogenes and promotes TNBC occurrence and development.

关 键 词：血管抑制蛋白2 三阴性乳腺癌 可变剪接 p53信号通路 细胞周期 

分 类 号：R737.9[医药卫生—肿瘤]