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Downregulated NM23-H1 expression is associated with intracranial invasion of nasopharyngeal carcinoma
1Faculty of Integrative Medicine, Traditional Chinese Medicine University of Hunan, Changsha, People's Republic of China.
Abstract:
Because the focus of nasopharyngeal carcinoma (NPC) is very close to intracranial organs, it often makes incursions into cranial cavity. Identification of intracranial invasion-associated indicators will provide potential therapeutic targets for NPC patients with intracranial invasion. In this regard, Human Xpro HC-plus cancer-related gene chip was utilised to screen intracranial invasion-associated genes for NPC from the biopsied primary focus tissue samples. In all, 8 upregulated and 23 downregulated genes were obtained. VEGF165 and MMP-9, the two upregulated genes, and NM23-H1, the downregulated one, were further confirmed by immunohistochemistry, quantitative real-time PCR and western blot. Invasion-associated cellular and nude mouse models were subsequently employed to study the biological properties of NM23-H1. NM23-H1 expression was significantly lower in 5-8F cells compared with that in 6-10B cells. Moreover, patch-clamp and transwell chamber were adopted to investigate the invading potential-associated biological dynamic mechanisms in the two cell lines, and Ca(2+) current and motility were significantly elevated in 5-8F cells compared with that in 6-10B cells. Berberine, an inhibitor of Ca(2+) current, could substantially increase the expression of NM23-H1 and decrease 5-8F cell motility. The specificity of berberine on NM23-H1 and cell motility was confirmed by RNAi assay.
Insights
This study identifies NM23-H1 as a potential biomarker for nasopharyngeal carcinoma (NPC) intracranial invasion. Lower NM23-H1 expression correlates with increased cell motility, suggesting therapeutic potential for berberine.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Nasopharyngeal carcinoma (NPC) can invade the cranial cavity due to its proximity to intracranial organs.
- Identifying intracranial invasion indicators is crucial for targeted NPC therapies.
Purpose of the Study:
- To screen for genes associated with intracranial invasion in NPC.
- To investigate the role of NM23-H1 in NPC invasion and its potential as a therapeutic target.
Main Methods:
- Human Xpro HC-plus cancer-related gene chip analysis.
- Immunohistochemistry, quantitative real-time PCR, and western blot for gene validation.
- Cellular and nude mouse models, patch-clamp, transwell assays, and RNA interference (RNAi) for functional studies.
Main Results:
- Screening identified 8 upregulated and 23 downregulated genes, including VEGF165, MMP-9, and NM23-H1.
- NM23-H1 expression was significantly lower in highly invasive NPC cells (5-8F) compared to less invasive cells (6-10B).
- Reduced NM23-H1 correlated with elevated Ca(2+) current and cell motility; berberine treatment increased NM23-H1 and decreased motility.
Conclusions:
- NM23-H1 is downregulated in NPC with intracranial invasion potential.
- NM23-H1 may serve as a prognostic biomarker for NPC intracranial invasion.
- Berberine's ability to modulate NM23-H1 and cell motility suggests therapeutic potential.
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