MicroRNA-5p and -3p Co-expression and Cross-targeting in Colon Cancer Cells
Overview
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Background: Two mature miRNA species may be generated from the 5' and 3' arms of a pre-miRNA precursor. In most cases, only one species remains while the complementary species is degraded. However, co-existence of miRNA-5p and -3p species is increasingly being reported. In this work, we aimed to systematically investigate co-expression of miRNA-5p/3p in colon cancer cells in a genome-wide analysis, and to examine cross-targeting of the dysregulated miRNAs and 5p/3p species.
Results: Four colon cancer cell lines were examined relative to two normal colon tissues. Of the 1,190 miRNAs analyzed, 92 and 36 were found to be up- or down-regulated, respectively, in cancer cells. Nineteen co-expressed miRNA-5p/3p pairs were further identified suggesting frequent 5p/3p co-accumulation in colon cancer cells. Of these, 14 pairs were co-up-regulated and 3 pairs were co-down-regulated indicating concerted 5p/3p dysregulation. Nine dysregulated miRNA pairs fell into three miRNA gene families, namely let-7, mir-8/200 and mir-17, which showed frequent cross-targeting in the metastasis process. Focusing on the let-7d-5p/3p pair, the respectively targeted IGF1R and KRAS were shown to be in a reverse relationship with expression of the respective miRNA, which was confirmed in transient transfection assays using let-7d mimic or inhibitor. Targeting of KRAS by let-7d was previous reported; targeting of IGF1R by let-7d-5p was confirmed in luciferase assays in this study. The findings of let-7d-5p/3p and multiple other miRNAs targeting IGF1R, KRAS and other metastasis-related factors suggest that 5p/3p miRNAs contribute to cross-targeting of multiple cancer-associated factors and processes possibly to evade functional abolishment when any one of the crucial factors are inactivated.
Conclusions: miRNA-5p/3p species are frequently co-expressed and are coordinately regulated in colon cancer cells. In cancer cells, multiple cross-targeting by the miRNAs, including the co-existing 5p/3p species, frequently occurs in an apparent safe-proof scheme of miRNA regulation of important tumorigenesis processes. Further systematic analysis of co-existing miRNA-5p/3p pairs in clinical tissues is important in elucidating 5p/3p contributions to cancer pathogenesis.
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Cione E, Michelini S, Abrego-Guandique D, Vaia N, Michelini S, Puleo V Curr Issues Mol Biol. 2024; 46(11):11957-11974.
PMID: 39590304 PMC: 11592672. DOI: 10.3390/cimb46110710.
Schonberg J, Borlak J Mol Cell Biochem. 2024; .
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Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.
Engin A, Engin A Adv Exp Med Biol. 2024; 1460:727-766.
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Gronau L, Duecker R, Jerkic S, Eickmeier O, Trischler J, Chiocchetti A Int J Mol Sci. 2024; 25(14).
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Molecular detection of exosomal miRNAs of blood serum for prognosis of colorectal cancer.
Bakhsh T, Alhazmi S, Farsi A, Yusuf A, Alharthi A, Qahl S Sci Rep. 2024; 14(1):8902.
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