Evidence map›Paper›PMID 41045405›Full record

ArticleMolecular biology reports2025

Voltage-Gated sodium channel Nav1.6 mediates glioblastoma proliferation and migration via Na

Samed Ahmed Alezzi Alameri, Yue Kong, Qing-Da Shi, Yue-Lin Huang, Ao-Ran Sui, Dan-Dan Zhu, Ying-Zi Wang, Wang Miao, Shao Li, Guang Yang

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In one paragraph

Article in Molecular biology reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Samed Ahmed Alezzi AlameriDepartment of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China.
Yue KongDepartment of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China.
Qing-Da ShiDepartment of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China.
Yue-Lin HuangDepartment of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China.
Ao-Ran SuiDepartment of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China.
Dan-Dan ZhuDepartment of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China.
Ying-Zi WangDepartment of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China.
Wang MiaoDepartment of Neurosurgery, First Hospital of Shanxi Medical University, Taiyuan, China. miaowang64@126.com.
Shao LiDepartment of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, Dalian Medical University, Dalian, 116044, China. lishao89@dmu.edu.cn.ORCID http://orcid.org/0000-0002-4889-8636
Guang YangDepartment of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yggts@tjh.tjmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlioblastoma (GBM) is an aggressive brain cancer with limited treatment options and a poor prognosis. Voltage-gated sodium channels, particularly Nav1.6 (SCN8A), have been implicated in tumor progression across various cancers. This study investigates the role of Nav1.6 in promoting GBM proliferation and migration via Na⁺/H⁺ exchanger-1 (NHE1), and its regulation of ERK and AKT signaling pathways to identify potential therapeutic strategies. METHODS AND

resultsImmunohistochemistry revealed high Nav1.6 expression in glioma tissues, peaking in grade IV GBM. Human GBM cell lines (U251, U138, U87) were used to explore the functional roles of Nav1.6 and NHE1 through siRNA-mediated silencing and pharmacological modulation. Quantitative PCR and Western blot confirmed the effective silencing of both targets and the downstream effects on protein expression. CCK8 and EdU DNA cell proliferation assays showed that inhibition of Nav1.6 or NHE1 significantly suppressed cell proliferation. Wound healing and Transwell migration assays demonstrated reduced cell motility upon gene silencing or treatment with TTX and EIPA. Flow cytometry and Caspase-3 analysis confirmed enhanced apoptosis following dual inhibition. Conversely, activation of Nav1.6 by ATXII promoted proliferation and migration, effects reversed by NHE1 downregulation. Importantly, combined suppression of Nav1.6 and NHE1 led to significant downregulation of phosphorylated AKT and ERK1/2, suggesting their cooperative role in modulating survival signaling in GBM.

conclusionNav1.6 promotes GBM progression by regulating ion homeostasis via NHE1 and activating AKT/ERK pathways. Dual targeting of Nav1.6 and NHE1 may offer a promising strategy to inhibit proliferation and induce apoptosis in GBM.

Indexed as

Brain NeoplasmsGlioblastomaNAV1.6 Voltage-Gated Sodium ChannelSodium-Hydrogen Exchanger 1ApoptosisCell Line, TumorCell MovementCell ProliferationGene Expression Regulation, NeoplasticHumansMAP Kinase Signaling SystemProto-Oncogene Proteins c-aktSignal TransductionNAV1.6 Voltage-Gated Sodium ChannelProto-Oncogene Proteins c-aktSCN8A protein, humanSLC9A1 protein, humanSodium-Hydrogen Exchanger 1ERK and AKT pathwayGlioblastomaNa+/H+ exchanger1 (NHE1)NaV1.6Voltage-gated sodium channels

Identifiers

PMID41045405

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.