肿瘤药学2023,Vol.13Issue(5):564-573,10.DOI:10.3969/j.issn.2095-1264.2023.05.06
TBL1XR1通过上调Wnt/β-catenin信号通路促进卵巢癌细胞迁移和侵袭
TBL1XR1 promotes the migration and invasion of ovarian cancer cells by upregulating Wnt/β-catenin signaling pathway
摘要
Abstract
Objective To investigate the mechanism of transducin(β)-like 1 X-linked receptor 1(TBL1XR1)promoting the migration and invasion of ovarian cancer cell by upregulating the Wnt/β-catenin signaling pathway.Methods Differen-tial expression of TBL1XR1 in ovarian cancer and normal ovarian tissues was assessed by using the Gene Expression Profil-ing Interactive Analysis(GEPIA 2),immunohistochemistry and Western blotting methods.The correlation between TBL1XR1 and overall survival of ovarian cancer patients in the Cancer Genome Atlas(TCGA)database was evaluated.The GO and KEGG enrichment analysis of differentially expressed genes(DEG)between TBL1XR1 high and low expression groups were also performed to explore their bioinformatic functions.Wound healing assay and Transwell stromal gel inva-sion assay were used to determine the effect of TBL1XR1 on the migration and invasion ability of ovarian cancer cells,re-spectively.Rescue experiments were performed with Wnt3a,an activator of the Wnt/β-catenin signaling pathway.Western blotting was used to detect changes in Wnt/β-catenin signaling pathway protein expression levels after knockdown or over-expression of TBL1XR1.The effect of TBL1XR1 on the changes of Wnt/β-catenin signaling pathway activity was detected by TOP/FOP luciferase reporter assay.Results The expression level of TBL1XR1 in ovarian cancer tissues was higher than that in normal ovarian tissues,and the overall survival of ovarian cancer patients in the low expression group was higher than that in the high expression group.The results of GO analysis and KEGG analysis suggested that the biological func-tions of TBL1XR1 were related to hormone transport,hormone secretion,regulation of hormone secretion and peptide trans-port,and neuroactive ligand-receptor interactions.Knockdown of TBL1XR1 significantly inhibited the migration and inva-sion of ovarian cancer cell,and this effect could be reversed by Wnt3a.Overexpression of TBL1XR1 significantly increased the migration and invasion ability of ovarian cancer cells.When TBL1XR1 expression was downregulated,the activity of Wnt/β-catenin signaling pathway and its protein expression levels were subsequently reduced.Conclusion TBL1XR1 was highly expressed in ovarian cancer and was associated with the poor prognosis of ovarian cancer patients.TBL1XR1 could promote the migration and invasion of ovarian cancer cells by upregulating Wnt/β-catenin signaling pathway.It may play an important role in the tumorigenesis and development of ovarian cancer as a tumor promoter.关键词
转导蛋白(β)样1X连锁受体1/卵巢癌/Wnt/β-catenin信号通路/迁移和侵袭Key words
Transducin(β)-like 1 X-linked receptor 1/Ovarian cancer/Wnt/β-catenin signal pathway/Migration and invasion分类
医药卫生引用本文复制引用
张文雯,高阳,苏敏,蔡红兵..TBL1XR1通过上调Wnt/β-catenin信号通路促进卵巢癌细胞迁移和侵袭[J].肿瘤药学,2023,13(5):564-573,10.基金项目
国家自然科学基金面上项目(81972447). (81972447)