Background: miR-182-5p (miR-182) is an oncogenic microRNA (miRNA) found in different tumor types and one of\nthe most up-regulated miRNA in colorectal cancer (CRC). Although this microRNA is expressed in the early steps of\ntumor development, its role in driving tumorigenesis is unclear.\nMethods: The effects of miR-182 silencing on transcriptomic profile were investigated using two CRC cell lines\ncharacterized by different in vivo biological behavior, the MICOL-14h-tert cell line (dormant upon transfer into\nimmunodeficient hosts) and its tumorigenic variant, MICOL-14tum. Apoptosis was studied by annexin/PI staining and\ncleaved Caspase-3/PARP analysis. The effect of miR-182 silencing on the tumorigenic potential was addressed in a\nxenogeneic model of MICOL-14tum transplant.\nResults: Endogenous miR-182 expression was higher in MICOL-14tum than in MICOL-14h-tert cells. Interestingly, miR-\n182 silencing had a strong impact on gene expression profile, and the positive regulation of apoptotic process was\none of the most affected pathways. Accordingly, annexin/PI staining and caspase-3/PARP activation demonstrated\nthat miR-182 treatment significantly increased apoptosis, with a prominent effect in MICOL-14tum cells. Moreover, a\nsignificant modulation of the cell cycle profile was exerted by anti-miR-182 treatment only in MICOL-14tum cells,\nwhere a significant increase in the fraction of cells in G0/G1 phases was observed. Accordingly, a significant growth\nreduction and a less aggressive histological aspect were observed in tumor masses generated by in vivo transfer of\nanti-miR-182-treated MICOL-14tum cells into immunodeficient hosts.\nConclusions: Altogether, these data indicate that increased miR-182 expression may promote cell proliferation,\nsuppress the apoptotic pathway and ultimately confer aggressive traits on CRC cells.
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