lncRNA GAS5通过抑制MAPK/ERK信号通路阻断乳腺癌细胞的上皮-间质转化过程

lncRNA GAS5 blocks epithelial-mesenchymal transition of breast cancer cells by inhibiting MAPK/ERK signaling pathway

目的:探讨lncRNA GAS5对乳腺癌细胞恶性生物学行为的影响及相关机制。方法:采用qPCR检测lncRNA GAS5在乳腺癌组织中和细胞系中的表达差异;Transwell实验和划痕实验分别检测lncRNA GAS5对乳腺癌细胞侵袭和迁移的影响;Western blot检测lncRNA GAS5对EMT的影响以及潜在作用机制;裸鼠成瘤实验验证lncRNA GAS5对动物体内成瘤的影响。结果:与癌旁正常组织相比,lncRNA GAS5在乳腺癌组织中呈低表达,而且在MDA-MB-231细胞中的表达最低;lncRNA GAS5的上调显著减低了MDA-MB-231细胞的侵袭和迁移能力;lncRNA GAS5的过表达使MDA-MB-231细胞中的E-cadherin蛋白显著升高,而N-cadherin、Vimentin和Snail蛋白的表达显著降低,而使用MAPK/ERK信号通路的抑制剂U0126能抵消lncRNA GAS5对MDA-MB-231细胞EMT的影响;结论:lncRNA GAS5能通过抑制MAPK/ERK信号通路阻断乳腺癌细胞的上皮-间质转化过程。

Objective:To investigate the effect of lncRNA GAS5 on the malignant biological behavior of breast cancer cells and the related mechanism.Methods:The expression of lncRNA GAS5 in breast cancer tissues and cell lines was detected by qPCR.Transwell and scratch experiments were used to detect the effect of lncRNA GAS5 on the invasion and migration of breast cancer cells.Western blot was used to detect the effect of lncRNA GAS5 on EMT and potential mechanism.Nude mice tumorigenesis was used to verify the effect of lncRNA GAS5 on tumor formation in animals.Results:Compared with normal tissues adjacent to tumors,lncRNA GAS5 was expressed lowly in breast cancer tissues and it was the lowest in MDA-MB-231 cells.Upregulation of lncRNA GAS5 significantly reduced the invasion and migration abilities of MDA-MB-231 cells.Overexpression of lncRNA GAS5 significantly increased the E-cadherin protein in MDA-MB-231 cells,while the expression of N-cadherin,Vimentin,and Snail proteins was significantly reduced.When the inhibitor U0126 was used,the effect of lncRNA GAS5 on EMT of MDA-MB-231 cells could be counteracted.Conclusion:lncRNA GAS5 can block the epithelial-mesenchymal transition of breast cancer cells by inhibiting the MAPK/ERK signaling pathway.