ArticleCancer cell international2017
The role of REST and HDAC2 in epigenetic dysregulation of Nav1.5 and nNav1.5 expression in breast cancer.
Article in Cancer cell international, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 37 citations in OpenAlex.
- nNav1.5 mRNA Expression in Triple Negative and Non-Triple Negative Breast Cancer Patients Treated at Hospital Pakar Universiti Sains Malaysia.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Effects of NaCell biochemistry and biophysics · 2025Review
- Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications.Redox biology · 2024Review
- Epigenetic regulation of breast cancer metastasis.Cancer metastasis reviews · 2024Review
- Visualization of breast cancer-related protein synthesis from the perspective of bibliometric analysis.European journal of medical research · 2023Article
- Review
- From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.Cancers · 2022Review
- Identification of potent HDAC 2 inhibitors using E-pharmacophore modelling, structure-based virtual screening and molecular dynamic simulation.Journal of molecular modeling · 2022Article
- Discovering the Triad between Nav1.5, Breast Cancer, and the Immune System: A Fundamental Review and Future Perspectives.Biomolecules · 2022Review
- The Pharmacological and Structural Basis of the AahII-NaFrontiers in pharmacology · 2022Article
- Emerging Biomarkers and Targeted Therapies in Feline Mammary Carcinoma.Veterinary sciences · 2021Review
- Histone deacetylase 2 knockout suppresses immune escape of triple-negative breast cancer cells via downregulating PD-L1 expression.Cell death & disease · 2021Article
- Pharmacological and nutritional targeting of voltage-gated sodium channels in the treatment of cancers.iScience · 2021Review
- Influence of nNav1.5 on MHC class I expression in breast cancer.Journal of biosciences · 2021Article
- Perspectives on the Role of Histone Modification in Breast Cancer Progression and the Advanced Technological Tools to Study Epigenetic Determinants of Metastasis.Frontiers in genetics · 2020Review
- The Functional Role of Voltage-Gated Sodium Channel Nav1.5 in Metastatic Breast Cancer.Frontiers in pharmacology · 2020Review
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreased expression of voltage-gated sodium channels (VGSCs) have been implicated with strong metastatic potential of human breast cancer in vitro and in vivo where the main culprits are cardiac isoform Nav1.5 and its 'neonatal' splice variant, nNav1.5. Several factors have been associated with Nav1.5 and nNav1.5 gain of expression in breast cancer mainly hormones, and growth factors.
aimThis study aimed to investigate the role of epigenetics via transcription repressor, repressor element silencing transcription factor (REST) and histone deacetylases (HDACs) in enhancing Nav1.5 and nNav1.5 expression in human breast cancer by assessing the effect of HDAC inhibitor, trichostatin A (TSA).
methodsThe less aggressive human breast cancer cell line, MCF-7 cells which lack Nav1.5 and nNav1.5 expression was treated with TSA at a concentration range 10-10,000 ng/ml for 24 h whilst the aggressive MDA-MB-231 cells was used as control. The effect of TSA on Nav1.5, nNav1.5, REST, HDAC1, HDAC2, HDAC3, MMP2 and N-cadherin gene expression level was analysed by real-time PCR. Cell growth (MTT assay) and metastatic behaviors (lateral motility and migration assays) were also measured.
resultsmRNA expression level of Nav1.5 and nNav1.5 were initially very low in MCF-7 compared to MDA-MB-231 cells. Inversely, mRNA expression level of REST, HDAC1, HDAC2, and HDAC3 were all greater in MCF-7 compared to MDA-MB-231 cells. Treatment with TSA significantly increased the mRNA expression level of Nav1.5 and nNav1.5 in MCF-7 cells. On the contrary, TSA significantly reduced the mRNA expression level of REST and HDAC2 in this cell line. Remarkably, despite cell growth inhibition by TSA, motility and migration of MCF-7 cells were enhanced after TSA treatment, confirmed with the up-regulation of metastatic markers, MMP2 and N-cadherin.
conclusionsThis study identified epigenetics as another factor that regulate the expression level of Nav1.5 and nNav1.5 in breast cancer where REST and HDAC2 play important role as epigenetic regulators that when lacking enhances the expression of Nav1.5 and nNav1.5 thus promotes motility and migration of breast cancer. Elucidation of the regulatory mechanisms for gain of Nav1.5 and nNav1.5 expression may be helpful for seeking effective strategies for the management of metastatic diseases.
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