@Article{mcb.2019.04366,
AUTHOR = {Zahra Niki  Boroujeni, Atefeh  Shirkav, Seyed Ahmad  Aleyasin},
TITLE = {Epigenetic Modulations Induction Using DSCR1 Ectopic Expression in Breast Cancer Cells},
JOURNAL = {Molecular \& Cellular Biomechanics},
VOLUME = {16},
YEAR = {2019},
NUMBER = {1},
PAGES = {41--58},
URL = {http://www.techscience.com/mcb/v16n1/28630},
ISSN = {1556-5300},
ABSTRACT = {Today, prognosis, diagnosis and treatment of cancers are progressing with non-invasive methods, including investigation and modification of the DNA methylation profile in cancer cells. One of the effective factors in regulating gene expression in mammals is DNA methylation. Methylation alterations of genes by external factors can change the expression of genes and inhibit the cancer. In the present study, we investigated the effect of Down syndrome critical region 1 gene (<i>DSCR1</i>) ectopic expression on the methylation status of the <i>BCL-XL, ITGA6, TCF3, RASSF1A, DOK7, VIM</i> and <i>CXCR4</i> genes in breast cancer cell lines. The effect of <i>DSCR1</i> ectopic expression on cell viability in <i>MCF7, MDA-MB-468, MDA-MB-231</i> and <i>MCF10A</i> cell lines was evaluated using MTT assay after the cells treated by lentivirus vectors harboring <i>DSCR1</i> for 72 hours. Methylation status of <i>BCL-XL, ITGA6, TCF3, RASSF1A, DOK7, VIM</i> and <i>CXCR4</i> genes in breast cancer cell lines was assessed by Restriction Enzyme PCR (REP) method. Also, methylation changes of these genes in breast cancer cell lines after treatment by lentivirus vectors harboring <i>DSCR1</i> for 7 days were analyzed by REP method. To confirm the effect of <i>DSCR1</i> on methylation of genes, Real-time PCR was performed. The MTT assay results indicated that <i>DSCR1</i> ectopic expression reduced cell viability in all three human breast cancer cell lines. Our results showed that <i>DSCR1</i> ectopic expression after 6 days reversed the hypomethylation status of the <i>BCL-XL, ITGA6, TCF3, VIM</i> and <i>CXCR4</i> genes and hypermethylation of <i>RASSF1A</i> and <i>DOK7</i> genes. The expression levels of <i>BCL-XL, ITGA6, TCF3, VIM</i> and <i>CXCR4</i> mRNA significantly reduced (<i>P</i><0.05) and the expression levels of <i>RASSF1A</i> and <i>DOK7</i> mRNA significantly increased (<i>P</i><0.05). Our findings reveal for the first time the impact of <i>DSCR1</i> ectopic expression on the methylation status of breast cancer cells and identify a novel agent for epigenetic therapy.},
DOI = {10.32604/mcb.2019.04366}
}