Objective To investigate the expression of transient receptor polycystic protein 2(TRPP2)in oral squamous epithelial cell and its effect on the invasion and migration of oral squamous cell carcinoma(OSCC),and to explore the potential signaling pathway of TRPP2 affecting OSCC metastasis.Methods The OSCC model with TRPP2 knockdown was constructed by CRISPR-Cas9 lentivirus plasmid transfection technique.The effect of TRPP2 protein knockdown was verified by Western blot.The effect of TRPP2 on OSCC proliferation was detected by CCK-8 assay and clone formation assay.RT-qPCR was used to detect the target genes associated with TRPP2 metastasis to OSCC.Western blot and RT-qPCR were used to detect the expression of EpCAM and its transcription factors as-sociated with unfolded protein response(UPR).The effects of TRPP2 on the invasion and migration of OSCC were examined by invasion test and scratch test.Results Compared with HOK in oral epithelial cells,the expression of TRPP2 in OSCC was significantly higher.When TRPP2 was knocked down,OSCC proliferation and clonal formation were significantly enhanced.Compared with the control group,a total of 494 differential genes were sig-nificantly expressed in TRPP2 knockdown transcription profile,among which 234 genes were up-regulated and 260 genes were down-regulated.The expression of EpCAM gene,which is related to cell adhesion,was up-regulated.In addition,UPR related genes PERK,ATF6,GRP78 were up-regulated,while ATF6 and EpCAM were down-reg-ulated in OSCC compared to HOK cells.The expression of ATF6 and EpCAM in oral squamous cell carcinoma cells was up-regulated by TRPP2 knockdown,and the cell migration and invasion ability decreased.The ATF6 inhibitor ceapin-A7(5 μmol/L)restored the OSCC migration and invasion ability of TRPP2 knockdown.Conclusion TR-PP2 is highly expressed in OSCC.When TRPP2 is knocked down,OSCC proliferation ability is enhanced,migra-tion and invasion ability are inhibited.TRPP2 mediates the expression of EpCAM through activation of UPR,thus affecting the invasion and migration of oral squamous cell carcinoma.
关键词
口腔鳞状细胞癌/瞬时受体多囊蛋白2/未折叠蛋白反应/内质网应激/上皮细胞黏附分子/细胞迁移和侵袭
Key words
oral squamous cell carcinoma/transient receptor potential polycystic 2/unfolded protein response/endoplasmic reticulumepithelial stress/cell adhesion molecule/cell migration and invasion
维普
万方数据