Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells

Abstract

Abstract. In the present study, we designed and conducted a series of assays to determine the expression of voltage-gated sodium channel (VGSC) neonatal isoform Nav1.5 (nNav1.5) in human brain astrocytoma and its effect on the proliferation, migration, invasion and apoptosis of astrocytoma U251 cells. The results showed that nNav1.5 mRNA and protein were expressed in both human brain astrocytoma and normal brain tissues, but their expression levels in astrocytoma were significantly higher (P<0.05). In astrocytomas, nNav1.5 mRNA and protein levels were also different (P<0.05) and were correlated with pathological grades. The immunofluorescence confocal microscopy observations demonstrated that nNav1.5 protein was expressed in the nucleus, cytoplasm and membrane of the astrocytoma cells. After transfection, the small interfering RNA (siRNA) targeted to nNav1.5 significantly reduced the expression levels of SCN5A/nNav1.5 mRNA and protein by 57.2% (P<0.05) and 66.6% (P<0.05), respectively. The MTT, wound healing, Matrigel invasion and flow cytometric assays confirmed that following siRNA downregulation of the expression of the SCN5A/nNav1.5 gene, the in vitro proliferation and in vitro invasiveness of the U251 cells were significantly reduced (P<0.05 for both comparisons), and the apoptosis rate was significantly increased (P<0.05). These results revealed that nNav1.5 expression in human brain astrocytoma was upregulated, and its expression was positively correlated with the degree of malignancy. Additionally, reduced nNav1.5 expression significantly suppressed the proliferation and invasiveness of astrocytoma cells, indicating a new target in the molecular diagnosis and therapy of astrocytoma.

Voltage‐gated sodium channel Nav1.7 promotes gastric cancer progression through MACC1‐mediated upregulation of NHE1

“…Previous studies showed that VGSCs control tumor growth and metastasis, and tumor cell invasion but not proliferation in non‐small cell lung cancer, breast cancer, colon cancer and cervical cancer . However, other reports indicate that VGSCs control cell invasion as well as proliferation in astrocytoma and prostate cancer, which is consistent with our results. Here, we shed light on the role of Na v 1.7 in promoting both invasion and proliferation of GC cells, which may be due to the specificity of different cancers.…”

Multiple Nav1.5 isoforms are functionally expressed in the brain and present distinct expression patterns compared with cardiac Nav1.5

“…However, the present study, in accordance with data from previous studies, demonstrated that Nav1.5 was expressed in various mammalian tissues including the brain, neuronal cell lines (2–14), dorsal root ganglia (DRG) (15–17), gastrointestinal tract (18), and various tumor tissues and cell lines (19–32), in addition to its established presence in cardiac tissue. Currently, a total of nine distinct Nav1.5 channel isoforms, Nav1.5a-f and the truncated variants Nav1.5 E28B-D, have been identified.…”

“…Therefore, the present study, in accordance with previous studies, selected the terminology ‘Nav1.5e’ rather than ‘neonatal Nav1.5’ to describe this splicing variant in normal tissues. Conversely, numerous authors decide to use the terminology ‘neonatal Nav1.5’ when investigating the expression of Nav1.5 in tumor cell lines (8,23,27,29,32), as ‘neonatal’ is there used to represent the re-expression of an embryonic gene or oncogene and its expression is associated with the occurrence and development of tumors.…”

Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model

“…Furthermore, the anti-ELTD1 treatment worked to down-regulate SCN5A, TRPM8 and BMP2, which were all shown to increase glioma cell proliferation, migration and invasion [48][49][50]. Therefore, suggesting that ELTD1 has a more complex relationship with Notch1 than previously understood.…”