MMP9 gene expression regulation by intragenic epigenetic modifications in breast cancer

被引:37
|
作者
Klassen, Liliane M. B. [1 ]
Chequin, Andressa [1 ]
Manica, Graciele C. M. [1 ]
Biembengut, Isis V. [1 ]
Toledo, Mariana B. [1 ]
Baura, Valter A. [2 ]
Pedrosa, Fabio de O. [2 ]
Ramon, Edneia A. S. [1 ]
Costa, Fabricio F. [3 ]
de Souza, Emanuel M. [2 ]
Klassen, Giseli [1 ]
机构
[1] Univ Fed Parana, Basic Pathol Dept, Curitiba, Parana, Brazil
[2] Univ Fed Parana, Biochem & Mol Biol Dept, Curitiba, Parana, Brazil
[3] Univ Catolica Brasilia, Genom Sci & Biotechnol Program, Brasilia, DF, Brazil
关键词
MMP-9; DNA methylation; Histone modifications; Intragenic region; Expression; Breast cancer; DNA METHYLATION; MATRIX METALLOPROTEINASES; UP-REGULATION; DEMETHYLATION; HISTONE; HYPERMETHYLATION; DIFFERENTIATION; LANGUAGE; INVASION;
D O I
10.1016/j.gene.2017.11.054
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women worldwide. Metastasis remains a major challenge for the clinical management and prognosis of patients with cancer. The metalloprotease MMP-9 plays a critical role in the first step of metastasis through extracellular matrix degradation. In this study, our goal was to determine the effect of epigenetic mechanisms in the promoter and intragenic region of this gene and to correlate it to the levels of expression of MMP9 in breast cancer cell lines. We have identified that MMP9 was highly expressed in the breast cancer cell lines MCF7 and MDA-MB-436 after 5-aza-2'-deoxycytidine (5-azadC) treatment. Sequencing of the promoter region as well as the CGI intronic CpG islands showed a specific sequence in CGI2, between CpGs 12-30 that was demethylated after 5-azadC treatment. This specific region was studied in breast cancer samples that revealed similar results with demethylation in positive MMP-9 breast cancer samples. Furthermore, the histone methylation marker of open chromatin (H3K4me3) was found in the promoter and intronic regions of MMP9 after 5-azadC treatment. Taken together these results showed a mechanism of DNA methylation and gene expression regulation by epigenetic marks present in the intronic DNA region of MMP9.
引用
收藏
页码:461 / 466
页数:6
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