Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects upper and lower motor neurons. Approximately 30% of patients have a mutation in one of
33 disease-causing genes, while disease development in others is probably due to the combination of various epigenetic factors. In this thesis, we analysed the expression of circular RNAs (circRNAs), micro RNAs (miRNAs), their host genes, and the
methylation levels of selected CpG sites in promoter regions of intergenic miRNAs. Using microarrays and subsequent validation of its results, we discovered six upregulated (hsa_circ_0000567, hsa_circ_0005218, hsa_circ_0035796, hsa_circ_0043138, hsa_circ_0063411, and hsa_circ_0088036) and one downregulated (hsa_circ_0023919) circRNA in leukocyte samples of ALS patients.
Hsa_circ_0023919, hsa_circ_0063411, and hsa_circ_0088036 were identified as the most promising biomarkers. Expression levels of three host genes, PICALM (hsa_circ_0023919), SUSD1 (hsa_circ_0088036), and AATK (miR-657), showed no difference between patients and healthy controls, while TNRC6B (hsa_circ_0063411) was upregulated in patients. Methylation levels of selected CpG sites in promoter regions of intergenic miRNAs miR-182, miR-217, and miR-451a does not affect their
expression levels. MiR-182 and miR-451a were upregulated and due to nonspecific qPCR products we were unable to determine miR-217 and miR-657 expression levels. CircRNA expression showed weak to moderate negative correlation with several clinical characteristics of ALS patients and moderate to strong correlation with expression levels of other circRNAs We observed a weak negative correlation between expression of miR-182 and expression of its predicted target gene TNRC6B, while no correlation was observed between the expression of miRNAs and their predicted target circRNAs.