| Abstract [eng] |
miRNAs are non-coding RNAs and are involved in the post-transcriptional regulation of gene expression. Various pathologies usually are characterized by altered miRNA expression profiles. Therefore, miRNAs can be used as biomarkers for disease diagnosis. Hence, miRNAs have a huge potential for applications during clinical practice. We identified that miRNAs are differentially expressed in ascending thoracic aortic aneurysm tissues and blood plasma samples compared with healthy samples by high-throughput sequencing. We detected, that differentially expressed miRNAs may regulate the TGF-β signaling pathway and the increase of transcription factor KLF4 expression in a part of cells. During the canonical miRNA biogenesis pathway, the miRNAs are cleaved by Drosha and Dicer ribonucleases. However, during alternative biogenesis pathway miRNAs can be produced in Drosha or Dicer independent manner. It was shown, that miRNA can be located in short introns, termed mirtrons. These mirtrons are spliced and appear to bypass Drosha cleavage. However, only a few mirtrons biogenesis were experimentally proven to be directly depended on splicing. We identifed that the biogenesis of only a part of bioinformatically predicted mirtrons is dependent on splicing. Moreover, we determined that splicing factors SRSF1 and SRSF2 promote mirtronic miRNA biogenesis. Finally, we identified that mirtronic miRNAs were differentially expressed in the digestive system cancer cell lines and tumors. |
