Determination of miRNAs related to autoimmune thyroid diseases by in silico methods

Autoimmune Thyroid Diseases (AITDs) are the most common organ-specific autoimmune disorders, in which immune system attacks thyroid gland. Both genetic (80%) and environmental factors (20%) contribute to the onset and development of AITDs. It has been determined many microRNAs (miRNAs) expressed differently in the regulation of genes related to autoimmune diseases, Graves' disease (GD) and Hashimoto's thyroiditis (HT) which are the most common AITDs. miRNAs are small non-coding RNAs, regulating gene expression at post-transcriptional level. It is aimed to identify novel miRNA sequences associated with autoimmune thyroid diseases by in silico methods. For this purpose, after obtaining the human reference miRNA sequences from miRBase database, BLAST analyses were performed between seven genes (TNFSF4, BACH2, DIO2, SLC25A16, JAKMIP2, TG, ZFAT-AS1) known to be associated with AITD and reference miRNAs. The secondary structures of the pre-miRNA sequences were determined by using the obtained data via RNAfold Web Server program. Target genes of pre-miRNAs and metabolic pathways of these target genes were identified by using RNAHybrid and BLAST2GO programs, respectively. A total of thirty-three novel miRNA sequences associated with the above-mentioned genes were identified for the first time. These miRNAs are hsa-miR376 for TNFSF4, hsa-miR6780 for BACH2, hsa-miR5010 for DIO2, hsa-miR320 for SLC25A16, hsa-miR4458 for JAKMIP2, hsa-miR576 for TG, related to ZFAT-AS1 including hsa-miR576, hsa-miR320, hsa-miR1321, hsa-miR2114, hsa-miR4640, hsa-miR6508, hsa-miR4458, hsa-miR4458, hsa-miR5011, hsa-miR581, hsa-miR4522, hsa-miR4522, hsa-miR361, hsa-miR511, hsa-miR122, hsa-miR147, hsa-miR337, hsa-miR7113, hsa-miR6886, hsa-miR6779, hsa-miR6779, hsa-miR6732, hsa-miR548, hsa-miR760, hsa-miR505, hsa-miR3156 ve hsa-miR4661. It was determined that target genes play roles in different pathways such as stress response, positive regulation of immune system process and production of inflammatory response. Moreover, KEGG results also indicated that these genes play important roles in forty-one different metabolic pathways such as autoimmune thyroid disease, thyroid hormone signalling, thyroid hormone synthesis, tyrosine metabolism, and thyroid cancer. This thesis is the first detailed study in which novel miRNA families and their targets were identified by using seven genes known to be associated with AITD via in silico analysis.