Abstract:
BACKGROUND:Increased 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. AIM:This 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). METHODS:The 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. RESULTS:mRNA 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. CONCLUSIONS:This 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.
journal_name
Cancer Cell Intjournal_title
Cancer cell internationalauthors
Kamarulzaman NS,Dewadas HD,Leow CY,Yaacob NS,Mokhtar NFdoi
10.1186/s12935-017-0442-6subject
Has Abstractpub_date
2017-08-01 00:00:00pages
74issn
1475-2867pii
442journal_volume
17pub_type
杂志文章abstract:Background:Tumor necrosis factor-a-induced protein 8 (TNFAIP8) presented a elevated expression in endometrial cancer (EC). However, the relationship of TNFAIP8 gene polymorphisms with EC risk remains unclear. This case-control study aimed to investigate the effect of single nucleotide polymorphisms (SNPs) in TNFAIP8 on...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0827-9
更新日期:2019-04-23 00:00:00
abstract:Background:Thyroid cancer is the most common type of endocrine malignancy and the incidence rate is rapidly increasing worldwide. Epigallocatechin-3-gallate (EGCG) could suppress cancer growth and induce apoptosis in many types of cancer cells. However, the mechanism of action of EGCG on the growth of human thyroid car...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0762-9
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0957-0
更新日期:2019-09-11 00:00:00
abstract:Background:Acute myeloid leukemia (AML) is a clinically and biologically heterogeneous disease. The survival of older patients is generally poor. In the current study, we sought to investigate the differences in molecular gene mutations between younger and older AML patients, and to identify those newly diagnosed AML p...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0716-7
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journal_title:Cancer cell international
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doi:10.1186/s12935-019-0900-4
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01649-2
更新日期:2020-12-09 00:00:00
abstract::Prostate cancer is a gland tumor in the male reproductive system. It is a multifaceted and genomically complex disease. Transmembrane protease, serine 2 and v-ets erythroblastosis virus E26 homolog (TMPRSS2-ERG) gene fusions are the common molecular signature of prostate cancer. Although tremendous advances have been ...
journal_title:Cancer cell international
pub_type: 杂志文章,评审
doi:10.1186/1475-2867-14-34
更新日期:2014-04-17 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-7-7
更新日期:2007-05-02 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01616-x
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journal_title:Cancer cell international
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doi:10.1186/s12935-020-01461-y
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0973-0
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pub_type: 杂志文章
doi:10.1186/s12935-019-0754-9
更新日期:2019-02-14 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0693-x
更新日期:2018-12-04 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-1087-4
更新日期:2020-01-10 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01485-4
更新日期:2020-10-19 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-6-16
更新日期:2006-05-31 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01537-9
更新日期:2020-09-09 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-016-0376-4
更新日期:2017-01-05 00:00:00
abstract::[This corrects the article DOI: 10.1186/s12935-019-0742-0.]. ...
journal_title:Cancer cell international
pub_type: 杂志文章,已发布勘误
doi:10.1186/s12935-019-0797-y
更新日期:2019-04-11 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-019-0860-8
更新日期:2019-05-22 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/1475-2867-13-54
更新日期:2013-06-01 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-017-0457-z
更新日期:2017-10-04 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-015-0214-0
更新日期:2015-06-18 00:00:00
abstract::[This retracts the article DOI: 10.1186/s12935-015-0237-6.]. ...
journal_title:Cancer cell international
pub_type: 撤回出版物
doi:10.1186/s12935-016-0359-5
更新日期:2016-11-04 00:00:00
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journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-018-0599-7
更新日期:2018-07-20 00:00:00
abstract:BACKGROUND:The aim of this study is to explore the expression of alpha-synuclein (α-synuclein) in benign, atypical, and anaplastic meningiomas and determine its role in the malignant progression of meningiomas. METHODS:Expression of α-synuclein was measured in 44 meningioma samples by real-time PCR analysis. The effec...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-016-0361-y
更新日期:2016-11-15 00:00:00
abstract:Background:Thyroid cancer (TC) is the most frequent endocrine malignancy. Long noncoding RNAs (lncRNAs) have been confirmed to act as significant roles in tumor development. The role of lncRNA TMPO-AS1 in TC is still unclear, so it remains to be explored. The aim of the research is to investigate the role and regulator...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01334-4
更新日期:2020-07-08 00:00:00
abstract:Background:Recent studies have demonstrated that the kallikrein and kallikrein-related peptidases (KLKs) exhibit aberrant expression in patients with colorectal cancer (CRC) and might be considered as potential prognostic biomarkers of CRC. However, inconsistent findings have been reported, which promote us to summariz...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-01350-4
更新日期:2020-06-22 00:00:00
abstract::Sineoculis homeobox homolog 1 (Six1), normally a developmentally restricted transcriptional regulator, is frequently dysregulated in mutiple cancers. Increasing evidences show that overexpression of Six1 plays a key role in tumorigenesis. However, the Six1 expression status and its relationship with the clinicopatholo...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-015-0215-z
更新日期:2015-06-20 00:00:00
abstract:Background:Abnormally expressed circular RNAs (circRNAs) are implicated in the development and treatment of gastric cancer (GC). Previous study has reported that hsa_circ_0003159 is expressed in GC. However, the role and mechanism of hsa_circ_0003159 in GC progression remain unclear. Methods:GC tissues and normal tiss...
journal_title:Cancer cell international
pub_type: 杂志文章
doi:10.1186/s12935-020-1119-0
更新日期:2020-02-19 00:00:00