Objective To explore the effect of neuregulin 4(NRG4)on proliferation,migration and invasion of glioma cells.Methods Reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression levels of NRG4 and human epidermal growth factor receptor 4(ErbB4)in the sera of glioma patients(study group)and healthy volunteers at the period(control group)as well as in glioma cell lines U251,SHG44,LN229,and T98G.U251 cells were divided into Control group(blank control),NC group(transfection with plasmid without carrying RNA),si-NRG4 group(transfection with si-NRG4),and si-NRG4+ErbB4 group[transfection with si-NRG4+overexpressing plasmids(pcDNA-ErbB4)].Cell counting kit-8(CCK-8)kit was used to assay cell proliferation.Wound healing and Transwell experiments were used to analyze the changes in U251 cell migration and invasion capacity.Western blot was used to detect the expression levels of key proteins such as phosphatidylinositol-3(PI3K)subunits p110α,p110β,phospho protein kinase B(pAKT;ser473 and thr308a),and AKT in PI3K/AKT pathway.Results The mRNA expression levels of NRG4 and ErbB4 in study group were significantly higher than those in control group(P＜0.0001).The relative expression levels of NRG4 and ErbB4 mRNA were the highest in glioma cell line U251 among the above glioma cell lines.When compared with NC group,NRG 4 gene expression was downregulated in si-NRG 4 group,leading to not only inhibiting cell proliferation,migration and invasion of U251 cells,but also reducing the protein expression levels of PI3K-p110α,pAKT-ser473,and pAKT-thr308(P＜0.05).Conclusion Inhibiting NRG4 expression may suppress the activation of PI3K/AKT pathway,U251 cell proliferation and migration,promote U251 cellular apoptosis.Therefore,NRG4 may be a potential target for glioma therapy.
维普
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