5’ isoforms of miR-1246 have distinct targets and stronger functions compared to canonical miR-1246 in colorectal cancer cells in vitro

Due to alternative processing pathway and post-transcriptional modifications, precursor miRNAs maturate into various sequence isoforms (isomiRs). These sequence variations may result in the changes of the miRNA seed site, target genes, involvement in signaling pathways and thus function. It is important to mention that knowledge about the targets of isomiR is still poor. To date, isomiR research has only been performed in melanoma, breast, and gastric cancer, but there are no experimental studies conducted in colorectal cancer. Here, we aimed to evaluate the putative targets and functional role in vitro of miR-1246 and its two 5’ isoforms (ISO-miR-1246_a and ISO-miR-1246_G). To our best knowledge, this is the first study showing the important role of 5’isoforms of miR-1246 in colorectal carcinogenesis, while acting on different targetomes and being involved in distinct signaling pathways. Commercial Caco-2 cells of CRC origin were analyzed for expression of WT-miR-1246 and its 5 isoforms using small RNA sequencing data and overabundance of the two miR-1246 isoforms was determined. This was followed by transcriptome analysis of Caco-2 cell transfected with WT-miR-1246, ISO-miR-1246_G and ISO-miR-1246_a mimics. This study includes Caco-2 cells with no transfection.