MicroRNA-326 contributes to autoimmune thyroiditis by targeting the Ets-1 protein.

Abstract

PURPOSE:

MicroRNA-326 (miR-326), as a member of the microRNA (miRNA) family, which includes endogenous single-stranded, conserved, noncoding small RNAs, has been reported to play important roles in autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus. However, few studies of the role of miR-326 in autoimmune thyroiditis (AIT) have been published. Here, we explored the roles of miR-326 and the involved pathway in iodine-induced AIT.

METHODS:

NOD.H-2h4 mice, which are a model of human AIT, were randomly divided into a normal water control group and a high-iodine group. Mice in the high-iodine group were administered 0.05% NaI (~1000 times the normal daily iodine intake), and mice in the control group received sterile water. Furthermore, we evaluated small interfering RNA (siRNA) interference in spleen mononuclear cell experiments in vitro.

RESULTS:

In this study, we found that Th17 cells were significantly increased with a high expression of miR-326 in an iodine-induced thyroiditis NOD.H-2h4 mouse model. In addition, the expression of Ets-1 protein, a negative regulator of Th17 differentiation, was significantly decreased. Intriguingly, our analysis showed that Ets-1 protein expression was negatively correlated with miR-326 levels in AIT mice (r = -0.814, p < 0.01). Our study indicated that miR-326 inhibited Ets-1 protein expression and promoted the differentiation of Th17 cells during the onset and development of AIT. The addition of a miR-326 inhibitor reversed Th17 cell production and Ets-1 protein expression, supporting this hypothesis.

CONCLUSIONS:

The results of our study suggest that miR-326 may target the Ets-1 protein to contribute to iodide-induced thyroiditis, providing a new theoretical basis for the use of miRNA targeting therapy for the treatment of autoimmune diseases.

• Authors: Na Zhao, Hongjin Zou, Jing Qin, Chenling Fan, Yongping Liu, Shuo Wang, Zhongyan Shan, Weiping Teng, Yushu Li
• Journal: Endocrine (Endocrine) Vol. 59 Issue 1 Pg. 120-129 (01 2018) ISSN: 1559-0100 [Electronic] United States
• PMID: 29181619 (Publication Type: Journal Article)

Chemical References

• Ets1 protein, mouse
• MIRN326 microRNA, mouse
• MicroRNAs
• Proto-Oncogene Protein c-ets-1
• Iodine

Topics

• Animals
• Disease Models, Animal
• Female
• Gene Expression Regulation
• Iodine
• Mice
• Mice, Inbred NOD
• Mice, Transgenic
• MicroRNAs (genetics, physiology)
• Proto-Oncogene Protein c-ets-1 (genetics)
• T-Lymphocytes, Regulatory (immunology, metabolism)
• Th17 Cells (immunology, metabolism)
• Thyroiditis, Autoimmune (chemically induced, genetics, immunology, metabolism)