CBX3通过STAT3信号通路调控乳腺癌细胞增殖、迁移

CBX3 regulates the proliferation and migration of breast cancer cells through the STAT3 signaling pathway

目的:检测多梳蛋白家族(PcG)中的染色体盒蛋白同源物3(CBX3)在乳腺癌细胞中的表达,了解CBX3对乳腺癌细胞增殖、迁移的影响。方法:通过TCGA数据库分析CBX3基因在非配对的乳腺癌组织和癌旁组织以及配对的乳腺癌组织和癌旁组织中的表达情况;WestemBlot检测CBX3在正常乳腺上皮细胞MCF-10A及乳腺癌细胞MDA-MB-231、SKBr3、MCF-7中的表达水平;选取MCF-7细胞为研究对象,分别构建CBX3基因过表达和沉默的细胞株,MTT、克隆形成实验、Transwell实验分别检测乳腺癌细胞增殖和迁移能力的变化;Western B1ot检测过表达和沉默CBX3基因后细胞增殖、迁移相关蛋白表达及STAT3信号通路相关蛋白的变化。结果:CBX3在乳腺癌组织中的表达高于癌旁组织(P<0.001).CBX3在乳腺癌细胞中表达高于正常乳腺上皮细胞(P<0.05);MTT实验及克隆形成实验证实,在MCF-7细胞中,高表达的CBX3增强了细胞的增殖能力,敲低CBX3则细胞增殖能力降低(P<0.05)。Transwell实验表明高表达CBX3使细胞迁移能力增强(P<0.05),敲低CBX3抑制了MCF-7细胞的迁移能力(P<0.05);CBX3沉默后,Vimentin、N-cadherin、p-JAK2、p-STAT3蛋白水平显著降低(P<0.05),E-cadherin水平明显升高(P<0.05)。结论:CBX3在乳腺癌中高表达,能够在体外促进乳腺癌细胞增殖和迁移,其作用机制可能与调控STAT3信号通路有关。这可能为乳腺癌的基因治疗提供了新思路。

Objective:To detect the expression of Chromobox protein homologue 3(CBX3)in breast cancer cells and to understand the effect of CBX3 on the proliferation and migration of breast cancer cells.Methods:The expression of CBX3 gene in unpaired breast cancer tissues and paracancerous tissues as well as paired breast cancer tissues and paracancerous tissues was analyzed by TCGA database.The expression levels of CBX3 in normal breast epithelial cells MCF-10A and breast cancer cells MDA-MB-231,SKBR3 and MCF-7 were detected by Western Blot.MCF-7 cells were selected as the research object,and cell lines with CBX3 gene overexpression and silencing were constructed respectively.The changes of proliferation and migration ability of breast cancer cells were detected by MTT,clone formation assay and Transwell assay,respectively.Cell proliferation and migration-related protein expression and protein changes related to STAT3 signaling pathway after overexpression and silenced CBX3 gene were detected by Western Blot.Results:The expression of CBX3 in breast cancer tissues was higher than that in paracancer tissues(P<0.001).The expression of CBX3 in breast cancer cells was higher than that in normal breast epithelial cells(P<0.05);MTT assay and clone formation assay demonstrated that in MCF-7 cells,overexpression of CBX3 enhanced cell proliferation,while knockdown of CBX3 reduced cell proliferation(P<0.05).Transwell assay showed that overexpression of CBX3 enhanced cell migration(P<0.05),knockdown of CBX3 inhibited the migration of MCF-7 cells(P<0.05);Vimentin,N-cadherin,p-JAK2,and p-STAT3 protein levels were significantly decreased after CBX3 silences(P<0.05),E-cadherin level was significantly increased(P<0.05).Conclusion:The high expression of CBX3 in breast cancer can promote the proliferation and migration of breast cancer cells in vitro,and the mechanism may be related to the regulation of STAT3 signaling pathway.This may provide new ideas for gene therapy for breast cancer.