TRPM7通过PI3K/AKT/ERK信号途径影响脑胶质瘤细胞增殖、上皮-间质转化

目的 探讨沉默M型顺时受体电位通道7（melastatin transient receptor potential channel 7，TRPM7）对脑胶质瘤细胞增殖、上皮-间质转化的影响及其作用机制。方法 采用qRT-PCR和Western blot检测TRPM7在人正常星形胶质HA1800细胞株以及脑胶质瘤细胞株（U251、U87、U373）中的表达。将U251细胞分为U251组（未转染的U251细胞）、U251/shNC组、U251/shTRPM7组，然后采用qRT-PCR和Western blot检测TRPM7的表达，细胞克隆形成实验检测细胞增殖能力；Transwell实验检测细胞迁移和侵袭能力；细胞免疫荧光实验检测E-cadherin和Vimentin表达情况；Western blot检测PI3K/AKT/ERK信号途径相关蛋白的表达情况。结果 与HA1800细胞比较，TRPM7在脑胶质瘤细胞系中高表达（P<0.05）；沉默TRPM7后，U251细胞中TRPM7表达降低（P<0.001），细胞增殖、迁移和侵袭能力明显下降（P<0.01）；E-cadherin表达增加（P<0.001），Vimentin表达降低（P<0.01）；PI3K蛋白表达水平下调（P<0.01），AKT和ERK1/2蛋白磷酸化程度明显降低（P<0.01）。结论 沉默TRPM7可抑制U251细胞增殖、迁移和侵袭能力及上皮-间质转化，其作用机制可能与激活PI3K/AKT/ERK信号途径有关。

TRPM7 affects the proliferation and epithelial-mesenchymal transition of brain glioma cells through PI3K/AKT/ERK signaling pathway

Objective To investigate the effect of silent melastatin transient receptor potential channel 7(TRPM7)on the proliferation and epithelial-mesenchymal transition of brain glioma cells and the underlying mechanism.Methods The TRPM7 expression in human normal astrocyte cell line HA1800 and glioma cell lines(U251,U87 and U373)were detected by qRT-PCR and Western blot.U251 cells were divided into the U251 group(untransfected U251 cells),U251/shNC group and U251/shTRPM7 group,then the expression of TRPM7 was detected by q RT-PCR and Western blot;the cell proliferation ability was detected by cell clone formation assay;the cell migration and invasion ability were detected by Transwell migration and invasion experiments;the expression of E-cadherin and Vimentin was detected by cellular immunofluorescence assay;the expression of PI3 K/AKT/ERK signaling pathway-related proteins were detected by Western blot.Results Compared with HA1800 cells,TRPM7 was highly expressed in glioma cell lines(P<0.05).Silencing TRPM7 reduced the expression of TRPM7 in U251 cells(P<0.001),and the ability of cell proliferation,migration and invasion were significantly reduced(P<0.01);E-cadherin expression was increased(P<0.001)and Vimentin expression was decreased(P<0.01);the expression level of PI3 K protein was down-regulated(P<0.01),and the phosphorylation level of AKT protein and ERK1/2 protein were also significantly reduced(P<0.01).Conclusion Silencing TRPM7 can inhibit the proliferation,migration,invasion ability and epithelial-mesenchymal transformation of U251 cells,which may be related to the PI3 K/AKT/ERK signaling pathway.