MicroRNA-409-3p通过靶向ZEB1促进HCMV感染的胶质瘤细胞迁移的机制研究

Mechanism of MicroRNA-409-3p Promoting the Migration of HCMV-Infected U87 Cells Through Targeting ZEB1

近年来的临床研究显示人巨细胞病毒(HCMV)与神经胶质瘤关系密切,但HCMV促进胶质瘤进展的机制仍未阐明,而microRNA(miRNA)在神经胶质瘤中被检测到异常表达,因此提出潜伏感染的HCMV会通过调节宿主细胞miRNA从而影响神经胶质瘤发生发展的假设。首先通过转录组分析和细胞实验,证实miR-409-3p在HCMV感染后显著下调。生物信息学预测显示锌指结合蛋白1(ZEB1)为其下游靶基因。miR-409-3p过表达后的细胞划痕实验以及Transwell迁移实验证实,miR-409-3p的过表达会导致ZEB1下调并抑制胶质瘤U87细胞迁移,而外源性过表达ZEB1可恢复U87细胞迁移能力。研究结果表明,潜伏感染的HCMV能够通过下调宿主细胞中miR-409-3p,从而上调ZEB1表达,促进神经胶质瘤细胞迁移。

In recent years,clinical studies have shown that human cytomegalovirus(HCMV)is closely related to glioma,but the mechanism by which HCMV promotes the progression of glioma has not yet been elucidated,and microRNA(miRNA)has been detected in glioma unusual expression.Therefore,it is hypothesized that latent infection of HCMV will affect the occurrence and development of glioma by regulating host cell miRNA.Firstly,transcriptome analysis and cell experiments confirmed that miR-409-3 p was significantly down-regulated after HCMV infection.Bioinformatics predictions show that zinc finger binding protein 1(ZEB1)is its downstream target gene.The Wound Healing assay and Transwell migration assay after miR-409-3 p overexpression confirmed thal the overexpression of miR-409-3 p can down-regulate ZEB1 and inhibit the migration of glioma U87 cells,while exogenous overexpression of ZEB1 can restore U87 cell migration ability.The results show that latently infected HCMV can down-regulate miR-409-3 p in host cells,thereby up-regulating the expression of ZEB1 and promoting the migration of glioma cells.