title: Expression of neonatal Nav1.5 in human brain astrocytoma and its effect on proliferation, invasion and apoptosis of astrocytoma cells.
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.
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Deguang
authors.initials: D
authors.lastname: Xing
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Shaowu
authors.initials: S
authors.lastname: Ou
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Yunjie
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qiu
authors.affiliation: Department of Neurosurgery, The First Hospital of China Medical University, Shenyang 110001, P.R. China.
authors.forename: Daling
authors.initials: D
authors.lastname: Ding
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, P.R. China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110001, P.R. China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Gao
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001254:Astrocytoma / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000096:biosynthesis* / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D034741:RNA, Small Interfering
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D034741:RNA, Small Interfering; C568320:SCN5A protein, human