摘要
Recent studies have shown that abnormal DNA methylation in CD4+ T cells plays essential roles in the development of systemic lupus erythematosus (SLE). Accumulated data suggest that miR-185 serves as critical regulators to control the methylation process in a variety of tumors. However, the role of miR-185 in T cell aberrant DNA hypomethylation of SLE still remains unclear. Therefore, this study was conducted to investigate whether miR-185 plays a role in the pregnancy associated with SLE. Our results revealed that miR-185 was significantly upregulated in CD4+ T cells from patients with pregnancy complicated with SLE and its degree of overexpression was inversely correlated with DNA methyltransferase 1 (DNMT1) mRNA levels. Target prediction analysis and dual luciferase reporter assays confirmed that DNMT1 was a direct target of miR-185. Furthermore, overexpression of miR-185 in CD4+ T cells from healthy donors led to the DNA hypomethylation and up-regulation of genes encoding CD11a and CD70, and inhibition of miR-185 expression in CD4+ T cells from patients with SLE caused reverse effects. This study indicated that miR-185 contributes to DNA hypomethylation of CD4+ T cells in pregnancies in patients with systemic lupus erythematosus by targeting DNA methyltransferase 1. Thus, miR-185 may represent a potential therapeutic target for SLE intervention.
- 出版日期2016
- 单位河北医科大学; 唐山市工人医院