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Nav1.5 is highly expressed in human glioma and promotes glioma cell migration and invasion
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Abstract:
Objective:To investigate the expression of voltage-gated sodium channels (VGSCs) alpha subunit, neonatal Nav1.5 (nNav1.5), in association with human glioma cell migration and invasion. Methods: Biopsy tumor specimens were collected from 68 patients who were diagnosed with glioma in China Medical University Hospital. Human glioma U251 cells were transfected transiently with an expression vector encoding nNav1.5. The mRNA abundance and protein content of nNav1.5 in both biopsy specimens and transfected U251 cells were assessed by real-time PCR and Western blotting respectively. The metastasis and invasion capacities of transfected U251 cells were assessed by wound healing assay and transwell invasion assay, respectively. Results: Neonatal Nav1.5 was positive in 72.6% of human glioma tissue specimens but only in 23.0% of normal tissue specimens (P<0.01). The expression of nNav1.5 was positively associated with the severity of glioma; 85.8% of WHO grade Ⅲ-Ⅳ gliomas were nNav1.5-positive and 52.9% of WHO grade Ⅰ-Ⅱ gliomas were nNav1.5-positive (P<0.01). Neonatal Nav1.5 silencing resulted in robust decreases in nNav1.5 mRNA and protein in U251 cells and significant inhibition of U251migration and invasion. Conclusion: Neonatal Nav1.5 is highly expressed in human glioma where it promotes glioma cell invasion and migration. Our findings suggest that nNav1.5 may serve as a novel diagnostic marker and/or therapeutic target for human glioma.
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Project Supported:
Project supported by the National Natural Science Foundation of China（No. 31100770）
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