剪切DR3第10外显子促进乳腺癌MDA-MB-231细胞株增殖

Cutting the tenth exon of DR3 promotes the proliferation of breast cancer cell line MDA-MB-231

目的探讨死亡受体3(DR3)第10外显子在乳腺癌中的表达与作用。方法利用基因表达谱交互分析数据库(GEPIA)分析DR3在乳腺癌中的表达和预后价值,运用log-rank检验进行生存差异比较。通过CRISPR/Cas9技术构建剪切DR3第10外显子的质粒载体,对三阴性乳腺癌细胞株(MDA-MB-231)DR3第10外显子进行剪切。分析DR3第10外显子剪切对MDA-MB-231细胞增殖和相关剪接变异体表达的影响。结果生物信息分析结果表明,DR3在乳腺癌患者中呈低表达,这种低表达预示总体生存期较短。剪切DR3第10外显子增强了DR3剪接变异体2、3、7的表达,并且这种改变伴随MDA-MB-231细胞增殖能力增强。结论DR3在乳腺癌患者中呈现低表达且预示患者总体生存期较短,DR3第10外显子与乳腺癌密切相关。

Objective To investigate the expression and role of the tenth exon of death receptor 3(DR3)in breast cancer cells.Methods Gene expression profiling interactive analysis(GEPIA)was used to analyze the expression and prognostic value of DR3 in breast cancer,and log-rank test was used to compare the survival differences.Construction of the plasmid vector splicing the tenth exon of DR3 was constructed and the tenth exon of DR3 in triple negative breast cancer cell line(MDA-MB-231)was knocked down using CRISPR/Cas9 technology.Results Bioinformatics analysis showed that DR3 expression was low in breast cancer patients,and low expression predicted poor overall survival.In vitro experiments revealed that knockdown of the tenth exon of DR3 enhanced the expressions of DR3 transcript variants 2,3 and 7,and this alteration resulted in enhanced proliferation of TNBC cell lines.Conclusion The low expression of DR3 in the patients with breast cancer is indicative of shorter overall survival,and the tenth exon of DR3 is closely related to breast cancer.