5′-Isoforms of miR-1246 Have Distinct Targets and Stronger Functional Impact Compared with Canonical miR-1246 in Colorectal Cancer Cells In Vitro

Medientyp: E-Artikel

Titel: 5′-Isoforms of miR-1246 Have Distinct Targets and Stronger Functional Impact Compared with Canonical miR-1246 in Colorectal Cancer Cells In Vitro

Beteiligte: Lukosevicius, Rokas; Alzbutas, Gediminas; Varkalaite, Greta; Salteniene, Violeta; Tilinde, Deimante; Juzenas, Simonas; Kulokiene, Ugne; Janciauskas, Dainius; Poskiene, Lina; Adamonis, Kestutis; Kiudelis, Gediminas; Kupcinskas, Juozas; Skieceviciene, Jurgita

Erschienen: MDPI AG, 2024

Sprache: Englisch

DOI: 10.3390/ijms25052808

ISSN: 1422-0067

Schlagwörter: Inorganic Chemistry ; Organic Chemistry ; Physical and Theoretical Chemistry ; Computer Science Applications ; Spectroscopy ; Molecular Biology ; General Medicine ; Catalysis

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Beschreibung: 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.

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