Abstract
Objectives: Neuregulin 4 (NRG4) is a novel signaling protein involved in many physiological activities. This study aims to explore role of NRG4 in glioma. Study design: Serum samples were obtained from patients with glioma, RT-qPCR assay was performed to detect the levels of NRG4 and ErbB4 in the patient's serum and glioma cell lines U251, SHG44, LN229 and T98G. The results suggested that the expression of NRG4 and ErbB4 were markedly higher in patients and glioma cell lines, especially in U251. Further, Small interfering RNAs (si-RNAs) that targeting NRG4 (si-NRG4) and the overexpressed plasmid of ErbB4 (pcDNA-ErbB4) were transfected into U251 cells. Cell proliferation was measured by CCK8 assay, migration and invasion was assessed by wound healing and transwell assays respectively. And the expression of PI3 K-p110 , PI3 K-p110 , pAKT-ser473, pAKT-thr308 and AKT were measured by western blot assay. Results: We found that downregulation of NRG4 significantly inhibited proliferation, migration and invasion of U251 cells. Moreover, NRG4 inhibition markedly reduced the expression of PI3 K-p110 , pAKT-ser473 and pAKT-thr308. And overexpression of ErbB4 alleviated the impact caused by NRG4 inhibition. Conclusion: NRG4 inhibition suppresses proliferation, migration and invasion of U251 via blocking the PI3 K/AKT pathway. NRG4 could serve as a potential target of glioma treatment.
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