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MicroRNA-5p and -3p Co-expression and Cross-targeting in Colon Cancer Cells

Overview
Journal J Biomed Sci
Publisher Biomed Central
Specialty Biology
Date 2014 Oct 8
PMID 25287248
Citations 52
Authors
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Abstract

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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References
1.
Slaby O, Svoboda M, Michalek J, Vyzula R . MicroRNAs in colorectal cancer: translation of molecular biology into clinical application. Mol Cancer. 2009; 8:102. PMC: 2780389. DOI: 10.1186/1476-4598-8-102. View

2.
Jiao L, Frampton A, Jacob J, Pellegrino L, Krell J, Giamas G . MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors. PLoS One. 2012; 7(2):e32068. PMC: 3284550. DOI: 10.1371/journal.pone.0032068. View

3.
Almeida M, Nicoloso M, Zeng L, Ivan C, Spizzo R, Gafa R . Strand-specific miR-28-5p and miR-28-3p have distinct effects in colorectal cancer cells. Gastroenterology. 2012; 142(4):886-896.e9. PMC: 3321100. DOI: 10.1053/j.gastro.2011.12.047. View

4.
Smits K, Paranjape T, Nallur S, Wouters K, Weijenberg M, Schouten L . A let-7 microRNA SNP in the KRAS 3'UTR is prognostic in early-stage colorectal cancer. Clin Cancer Res. 2011; 17(24):7723-31. PMC: 5919188. DOI: 10.1158/1078-0432.CCR-11-0990. View

5.
Lujambio A, Lowe S . The microcosmos of cancer. Nature. 2012; 482(7385):347-55. PMC: 3509753. DOI: 10.1038/nature10888. View