Abstract
MicroRNAs (miRNAs) are negative gene regulators acting at the 3′UTR level, modulating the translation of cancer-related genes. Single-nucleotide polymorphisms (SNPs) within the 3′UTRs could impact the miRNA-dependent gene regulation either by weakening or by reinforcing the binding sites. Thus, the alteration of the normal regulation of a given gene could affect the individual’s risk of cancer. Therefore, it is helpful to develop a tool enabling the researchers to predict which of the many SNPs could really impact the regulation of a target gene. At present, there are several available databases and algorithms able to predict potential binding sites in the 3′UTR of genes. However, each algorithm gives different predictions and none of them gives, for each polymorphism, a direct measurement of the biological impact. We propose an approach allowing the assignment to each polymorphism a ranking of its biological impact. The method is based on a simple elaboration of predictions from preexisting well-established algorithms. As an example, we show the application of this approach to 140 genes candidate for colorectal cancer (CRC). These genes were identified following a genome-wide sequencing of 20,857 transcripts from 18,191 genes in 11 CRC specimens and were found somatically mutated and thought to be crucial for the development of cancer.
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References
Bartel, D. P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function, Cell 116, 281–297.
Tomari, Y. and Zamore, P. D. (2005) Perspective: machines for RNAi, Genes Dev. 19, 517–529.
Sood, P., Krek, A., Zavolan, M., Macino, G., and Rajewsky, N. (2006) Cell-type-specific signatures of microRNAs on target mRNA expression, Proc. Natl. Acad. Sci. U. S. A. 103, 2746–2751.
Chen, K., Song, F., Calin, G., Wei, Q., Hao, X., and Zhang, W. (2008) Polymorphisms in microRNA targets: a gold mine for molecular epidemiology, Carcinogenesis 29, 1306–1311.
John, B., Enright, A. J., Aravin, A., Tuschl, T., Sander, C., and Marks, D. S. (2004) Human microRNA targets, PLoS Biol. 2, e363.
Wood, L. D., Parsons, D. W., Jones, S., Lin, J., Sjoblom, T., Leary, R. J., Shen, D., Boca, S. M., Barber, T., Ptak, J., Silliman, N., Szabo, S., Dezso, Z., Ustyanksky, V., Nikolskaya, T., Nikolsky, Y., Karchin, R., Wilson, P. A., Kaminker, J. S., Zhang, Z., Croshaw, R., Willis, J., Dawson, D., Shipitsin, M., Willson, J. K., Sukumar, S., Polyak, K., Park, B. H., Pethiyagoda, C. L., Pant, P. V., Ballinger, D. G., Sparks, A. B., Hartigan, J., Smith, D. R., Suh, E., Papadopoulos, N., Buckhaults, P., Markowitz, S. D., Parmigiani, G., Kinzler, K. W., Velculescu, V. E., and Vogelstein, B. (2007) The genomic landscapes of human breast and colorectal cancers, Science 318, 1108–1113.
Griffiths-Jones, S., Grocock, R. J., van Dongen, S., Bateman, A., and Enright, A. J. (2006) miRBase: microRNA sequences, targets and gene nomenclature, Nucleic Acids Res. 34, D140–D144.
Krek, A., Grun, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I, Gunsalus, K. C., Stoffel, M., and Rajewsky, N. (2005) Combinatorial microRNA target predictions, Nat. Genet. 37, 495–500.
Rusinov, V., Baev, V., Minkov, I. N., and Tabler, M. (2005) MicroInspector: a web tool for detection of miRNA binding sites in an RNA sequence, Nucleic Acids Res. 33, W696–W700.
Kiriakidou, M., Nelson, P. T., Kouranov, A., Fitziev, P., Bouyioukos, C., Mourelatos, Z., and Hatzigeorgiou, A. (2004) A combined computational–experimental approach predicts human microRNA targets, Genes Dev. 18, 1165–1178.
Lewis, B. P., Shih, I. H., Jones-Rhoades, M. W., Bartel, D. P., and Burge, C. B. (2003) Prediction of mammalian microRNA targets, Cell 115, 787–798.
Cummins, J. M., He, Y., Leary, R. J., Pagliarini, R., Diaz, L. A., Jr., Sjoblom, T., Barad, O., Bentwich, Z., Szafranska, A. E., Labourier, E., Raymond, C. K., Roberts, B. S., Juhl, H., Kinzler, K. W., Vogelstein, B., and Velculescu, V. E. (2006) The colorectal microRNAome, Proc. Natl. Acad. Sci. U. S. A. 103, 3687–3692.
Gruber, A. R., Lorenz, R., Bernhart, S. H., Neubock, R., and Hofacker, I. L. (2008) The Vienna RNA websuite, Nucleic Acids Res. 36, W70–W74.
Landi, D., Gemignani, F., Naccarati, A., Pardini, B., Vodicka, P., Vodickova, L., Novotny, J., Forsti, A., Hemminki, K., Canzian, F., and Landi, S. (2008) Polymorphisms within micro-RNA-binding sites and risk of sporadic colorectal cancer, Carcinogenesis 29, 579–584.
Acknowledgements
This work was, in part, funded by Associazione Italiana Ricerca Cancro (Italy) investigator grant 2008 and NCI (NIH-USA) Grant code R03CA115062, anno 2006–2008. Small grants in cancer epidemiology.
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Landi, D., Barale, R., Gemignani, F., Landi, S. (2011). Prediction of the Biological Effect of Polymorphisms Within MicroRNA Binding Sites. In: Wu, W. (eds) MicroRNA and Cancer. Methods in Molecular Biology, vol 676. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-863-8_14
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DOI: https://doi.org/10.1007/978-1-60761-863-8_14
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