Title 5′-isoforms of miR-1246 have distinct targets and stronger functional impact compared with canonical miR-1246 in colorectal cancer cells in vitro /
Authors Lukoševičius, Rokas ; Alzbutas, Gediminas ; Varkalaitė, Greta ; Šaltenienė, Violeta ; Tilindė, Deimantė ; Juzėnas, Simonas ; Kūlokienė, Ugnė ; Jančiauskas, Dainius ; Poškienė, Lina ; Adamonis, Kęstutis ; Kiudelis, Gediminas ; Kupčinskas, Juozas ; Skiecevičienė, Jurgita
DOI 10.3390/ijms25052808
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Is Part of International journal of molecular sciences.. Basel : MDPI. 2024, vol. 25, iss. 5, art. no. 2808, p. [1-18].. ISSN 1661-6596. eISSN 1422-0067
Keywords [eng] 5′-isomiR functions in vitro ; 5′-isomiRs ; CRC ; miR-1246 ; targetome
Abstract [eng] Colorectal cancer (CRC) is a multifactorial disease involving genetic and epigenetic factors, such as miRNAs. Sequencing-based studies have revealed that miRNAs have many isoforms (isomiRs) with modifications at the 3′- and 5′-ends or in the middle, resulting in distinct targetomes and, consequently, functions. In the present study, we aimed to evaluate the putative targets and functional role of miR-1246 and its two 5′-isoforms (ISO-miR-1246_a and ISO-miR-1246_G) in vitro. Commercial Caco-2 cells of CRC origin were analyzed for the expression of WT-miR-1246 and its 5′-isoforms using small RNA sequencing data, and the overabundance of the two miR-1246 isoforms was determined in cells. The transcriptome analysis of Caco-2 cells transfected with WT-miR-1246, ISO-miR-1246_G, and ISO-miR-1246_a indicated the minor overlap of the targetomes between the studied miRNA isoforms. Consequently, an enrichment analysis showed the involvement of the potential targets of the miR-1246 isoforms in distinct signaling pathways. Cancer-related pathways were predominantly more enriched in dysregulated genes in ISO-miR-1246_G and ISO-miR-1246_a, whereas cell cycle pathways were more enriched in WT-miR-1246. The functional analysis of WT-miR-1246 and its two 5′-isoforms revealed that the inhibition of any of these molecules had a tumor-suppressive role (reduced cell viability and migration and promotion of early cell apoptosis) in CRC cells. However, the 5′-isoforms had a stronger effect on viability compared with WT-miR-1246. To conclude, this research shows that WT-miR-1246 and its two 5′-isoforms have different targetomes and are involved in distinct signaling pathways but collectively play an important role in CRC pathogenesis.
Published Basel : MDPI
Type Journal article
Language English
Publication date 2024
CC license CC license description