DAI Xufang,YAN Xiaojing,XIE Peng,et al.Sodium valproate promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway [J].J Third Mil Med Univ,2020,42(12):1195-1200.

丙戊酸钠通过激活miR-148a-3p/Mcl-1通路促进SH-SY5Y细胞凋亡(/HTML )




Sodium valproate promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway
DAI Xufang YAN Xiaojing XIE Peng LIAN Jiqin

Faculty of Education for Children with Special Needs, 2Chongqing Key Laboratory of Psychological Diagnosis and Educational Technology for Children with Special Needs, College of Education Science, Chongqing Normal University, Chongqing, 400047; 3Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing, 400038, China

sodium valproate SH-SY5Y cells Mcl-1 miR-148a-3p apoptosis

目的探讨抗癫痫药丙戊酸钠(sodium valproate,VPA)对神经细胞的凋亡诱导作用及相关机制。方法将人神经母细胞瘤细胞(SH-SY5Y)用不同剂量VPA处理,流式分析细胞凋亡水平变化,Western blot检测Mcl-1蛋白水平变化,定量PCR分析Mcl-1 mRNA与miR-148a-3p水平变化,报告基因实验检测Mcl-1启动子活性变化。用miR-148a-3p抑制剂联合VPA处理细胞,观察miR-184a-3p在VPA下调Mcl-1表达中的作用及对VPA促SH-SY5Y细胞凋亡效果的影响。结果VPA可促进SH-SY5Y细胞凋亡,并抑制SH-SY5Y细胞中Mcl-1的蛋白和mRNA水平(P<0.05)。VPA处理不影响SH-SY5Y细胞中Mcl-1的启动子活性(P>0.05)。VPA可显著增强SH-SY5Y细胞中miR-148a-3p的表达(P<0.05),使用miR-148a-3p抑制剂可减轻VPA对Mcl-1表达的抑制作用,并减弱VPA的促细胞凋亡效果。结论VPA可能通过激活miR-148a-3p/Mcl-1信号通路促进SH-SY5Y细胞凋亡。


ObjectiveTo investigate the apoptosis-inducing effect of sodium valproate (VPA) on nerve cells and the underlying mechanism. MethodsHuman neuroblastoma SH-SY5Y cells treated with VPA of difterent doses were examined for apoptosis and Mcl-1 protein expression using flow cytometry and Western blotting, respectively. The  mRNA expression of Mcl-1 and miR-148a-3p in the treated cells was detected with qRT-PCR, and the promoter activity of Mcl-1 gene was analyzed using a reporter gene assay. The changes of cell apoptosis and Mcl-1 expression in SH-SY5Y cells were analyzed following combined treatment with VPA and a miR-148a-3p antagonist. ResultsVPA treatment significantly promoted apoptosis and down-regulated Mcl-1 expression at both the mRNA and protein levels in SH-SY5Y cells. VPA treatment did not significantly affect the transcriptional activity of Mcl-1 promoter but up-regulated the expression of miR-148a-3p in SH-SY5Y cells. The application of the miR-148a-3p antagonist obviously attenuated the inhibitory effect of VPA on Mcl-1 expression and VPA-induced apoptosis in the cells. ConclusionVPA promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway.


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 DAI Xufang,QIN Liyan,LIAN Jiqin.Sodium valprovate upregulates miR-34a to inhibit Bcl-2 expression in human neuroblastoma SHSY5Y cells in vitro[J].J Third Mil Med Univ,2018,40(12):1060.

更新日期/Last Update: 2020-06-19