Title : Daily profile in miRNA expression in the colon and their role in colorectal cancer

Colorectal cancer (CRC) belongs among the most frequently diagnosed malignancies and its progression is strongly influenced by miRNAs as well as the circadian system. With the use of high-throughput sequencing of miRNAs expressed in the rat colon during 24h light (L) dark (D) cycle 371 mature miRNAs and 442 pre-mature miRNAs (pre-miRNAs) was detected. Nearly 10 % of mature miRNAs showed a daily rhythm in expression of guide (66%) or passenger (33%) strand. Rhythm in expression was detected in 5% of pre-miRNAs. Mature and pre-miRNAs derived from one gene showed a high level of correlation. A peak of miRNA's levels was in the most cases observed during the first half of the D phase of LD cycle (D1). There was a pronounced trend to higher expression of DGCR8, during the D compared to L phase. Gene ontology enrichment analysis revealed that genes interfering with miRNAs with peak expression during D phase influence apoptosis, angiogenesis, immune system and EGF and TGF-beta signaling to higher extend compared to those with the maximum in L phase. Pro-apoptic role of miR-150-5p induction was demonstrated with the use of CRC cell line DLD1. miR-150-5p was shown to inhibit expression of oncogene cry1. Target genes of D1 and D2 miRNAs differently influenced Toll and Notch signaling pathways and hypoxia response via HIF activation. Results indicate that timing of miRNA expression can influence, via their target genes, specific molecular pathways involved in regulation of CRC progression. Research was supported by projects APVV-20-0241 and VEGA 1/0455/23.

Prof. Iveta Herichová DrSc. is focused on the role of the circadian system and miRNA interferences in progression of colorectal cancer. She also studies causes of sex-dependent differences in colorectal cancer incidence. She holds a PhD. in Animal Physiology from Slovak Academy of Sciences, P. J. Šafárik University, Slovak Republic. Previously she has worked in the Katholieke Universiteit Leuven and Belgium and Texas A&M University, USA. Recently she is engaged as professor at the Comenius University in Bratislava, Slovak Republic.