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Epigenetic Modulations Induction Using DSCR1 Ectopic Expression in Breast Cancer Cells

Zahra Niki Boroujeni1, Atefeh Shirkav1, Seyed Ahmad Aleyasin1,*
Medical Biotechnology Division, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, 14965/161, Iran.
* Corresponding Author: Seyed Ahmad Aleyasin. Email: .

Molecular & Cellular Biomechanics 2019, 16(1), 41-58. https://doi.org/10.32604/mcb.2019.04366

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 (DSCR1) ectopic expression on the methylation status of the BCL-XL, ITGA6, TCF3, RASSF1A, DOK7, VIM and CXCR4 genes in breast cancer cell lines. The effect of DSCR1 ectopic expression on cell viability in MCF7, MDA-MB-468, MDA-MB-231 and MCF10A cell lines was evaluated using MTT assay after the cells treated by lentivirus vectors harboring DSCR1 for 72 hours. Methylation status of BCL-XL, ITGA6, TCF3, RASSF1A, DOK7, VIM and CXCR4 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 DSCR1 for 7 days were analyzed by REP method. To confirm the effect of DSCR1 on methylation of genes, Real-time PCR was performed. The MTT assay results indicated that DSCR1 ectopic expression reduced cell viability in all three human breast cancer cell lines. Our results showed that DSCR1 ectopic expression after 6 days reversed the hypomethylation status of the BCL-XL, ITGA6, TCF3, VIM and CXCR4 genes and hypermethylation of RASSF1A and DOK7 genes. The expression levels of BCL-XL, ITGA6, TCF3, VIM and CXCR4 mRNA significantly reduced (P<0.05) and the expression levels of RASSF1A and DOK7 mRNA significantly increased (P<0.05). Our findings reveal for the first time the impact of DSCR1 ectopic expression on the methylation status of breast cancer cells and identify a novel agent for epigenetic therapy.

Keywords

Breast cancer, methylation, DSCR1, REP PCR.

Cite This Article

Boroujeni, Z. N., Shirkav, A., Aleyasin, S. A. (2019). Epigenetic Modulations Induction Using DSCR1 Ectopic Expression in Breast Cancer Cells. Molecular & Cellular Biomechanics, 16(1), 41–58.



This work is licensed under a Creative Commons Attribution 4.0 International License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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