DICER and DROSHA gene expression and polymorphisms in autoimmune thyroid diseases

Abstract

Dicer and Drosha are RNase III enzymes that are necessary for the biogenesis of most miRNAs. However, there are no reports on the association of Dicer and Drosha with the pathogenesis of autoimmune thyroid disease (AITD). We genotyped DICER rs3742330A/G and rs1057035T/C as well as DROSHA rs644236C/T and rs10719C/T polymorphisms in 255 Hashimoto's disease (HD) patients, in 255 Graves' disease (GD) patients and in 128 healthy controls by the polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method. We also examined the expression of DICER and DROSHA gene in peripheral blood mononuclear cells (PBMCs) by quantitative RT-PCR (qRT-PCR) methods. The TT genotype of the DICER rs1057035 polymorphism was less frequent in GD patients (p = 0.0098) than in healthy subjects. The CC genotype of DROSHA rs644236 polymorphism were more frequent in GD patients than in HD patients (p = 0.0171). The gene expression of DICER was lower in patients with AITD compared with that in control subjects (p = 0.0064) and was lower in patients with GD in remission than in patients with intractable GD (p = 0.0213). In addition, the expression of DROSHA was lower in patients with AITD than that in control subjects (p < 0.0001) and was lower in patients with severe HD than in patients with mild HD (p = 0.0440). In conclusion, the DICER rs1057035 TT genotype and DROSHA rs644236 CC genotype were associated with the development of GD and the differentiation between GD and HD, respectively. The expression levels of DICER and DROSHA genes were low in AITD and differed depending on the intractability of GD and the severity of HD, respectively.

Association of MicroRNA Biogenesis Genes Polymorphisms with Ischemic Stroke Susceptibility and Post-Stroke Mortality

“…Therefore, in this study of ischemic stroke, we focused on miRNA biogenesis genes, such as DICER1, DROSHA, XPO5 , and RAN , which are related to endothelial miRNA expression and angiogenesis [ 31 , 32 ]. We evaluated six polymorphisms in DICER1, DROSHA, XPO5 , and RAN genes essential for miRNA biosynthesis [ 33 - 35 ], in ischemic stroke cases and controls. We found that polymorphisms in DICER and DROSHA , both of which are involved in angiogenesis and coagulation mechanisms [ 36 - 38 ], were linked to ischemic stroke.…”

“…In addition, functional analysis of rs1057035, which resides in the 3’-UTR of DICER , has revealed that the polymorphism affects hsa-miR-574-3p targeting and DICER expression [ 50 ]. The DROSHA rs10719 polymorphism, which is located in the 3’-UTR of DROSHA , was associated with different DROSHA expression levels [ 33 ] and presented different binding efficiency for the target site of hsa-miR-27b [ 35 , 51 ]. Furthermore, previous studies reported that DROSHA rs6877842 and rs640831 polymorphisms affected miRNA expression levels [ 34 , 52 ].…”

The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

“…In addition, Dicer inactivation also increased the expressions of Tg and decreased the expressions of cell adhesion proteins in the thyroid cells, such as Cdh16 and Cdh1 (155). Saeki et al found that AITD patients had lower expression of Dicer and DROSHA compared with healthy controls, and DICER rs1057035 and DROSHA rs644236 were obviously associated with susceptibility to GD (156). …”

Downregulation of Drosha, Dicer, and DGCR8 mRNAs in Peripheral Blood Mononuclear Cells of Patients with Rheumatoid Arthritis

“…Results of a study have revealed downregulation of Drosha and Dicer in patients with Graves' disease and Hashimoto's disease, suggesting that low expression of these enzymes may cause reduced expression of miRNAs like miR-27b, miR-let7f, miR-21 and miR-98, which will increase the susceptibility to autoimmune thyroid disease [41]. Another study demonstrated significantly upregulation of Drosha, Dicer and DGCR8 in psoriasis patients in comparison with controls [42].…”