Abstract
MicroRNAs (miRNAs) are small, nonprotein-coding RNAs that negatively regulate their mRNA target genes in a sequence-specific manner. While their specific impact on biological processes and cellular functions remain largely unknown, dysregulated miRNAs have been implicated in numerous diseases, including cancers. Several large-scale profiling studies using tissue samples have revealed a consistent yet complex pattern of miRNA dysregulation in human cancer. In particular, global alteration of multiple miRNAs is common in human tumorigenesis. Systemic analysis of pathways and functions coregulated by these dysregulated miRNAs is a crucial step to understand the role of miRNAs in tumorigenesis. This chapter provides an integrated pipeline to identify cellular pathways and functions specifically regulated by multiple dysregulated miRNAs. Protocols described in this chapter include (1) miRNA target prediction using TargetScan algorithm, (2) data compilation to identify target genes coregulated by multiple miRNAs, and (3) pathway enrichment analysis of coregulated targets using MetaCore pathway and network database.
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References
Ambros, V. (2004) The functions of animal microRNAs, Nature 431, 350–355.
Bartel, D. P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function, Cell 116, 281–297.
Calin, G. A., Sevignani, C., Dumitru, C. D., Hyslop, T., Noch, E., Yendamuri, S., Shimizu, M., Rattan, S., Bullrich, F., Negrini, M., and Croce, C. M. (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers, Proceedings of the National Academy Sciences of United States of America 101, 2999–3004.
Lu, J., Getz, G., Miska, E. A., Alvarez-Saavedra, E., Lamb, J., Peck, D., Sweet-Cordero, A., Ebert, B. L., Mak, R. H., Ferrando, A. A., Downing, J. R., Jacks, T., Horvitz, H. R., and Golub, T. R. (2005) MicroRNA expression profiles classify human cancers, Nature 435, 834–838.
Chen, C. Z. (2005) MicroRNAs as oncogenes and tumor suppressors, New England Journal of Medicine 353, 1768–1771.
Croce, C. M. (2008) Oncogenes and cancer, New England Journal of Medicine 358, 502–511.
Bloomston, M., Frankel, W. L., Petrocca, F., Volinia, S., Alder, H., Hagan, J. P., Liu, C. G., Bhatt, D., Taccioli, C., and Croce, C. M. (2007) MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis, JAMA 297, 1901–1908.
Bottoni, A., Zatelli, M. C., Ferracin, M., Tagliati, F., Piccin, D., Vignali, C., Calin, G. A., Negrini, M., Croce, C. M., and Degli Uberti, E. C. (2007) Identification of differentially expressed microRNAs by microarray: a possible role for microRNA genes in pituitary adenomas, Journal of Cellular Physiology 210, 370–377.
Chen, H. C., Chen, G. H., Chen, Y. H., Liao, W. L., Liu, C. Y., Chang, K. P., Chang, Y. S., and Chen, S. J. (2009) MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma, British Journal of Cancer 100, 1002–1011.
Ciafre, S. A., Galardi, S., Mangiola, A., Ferracin, M., Liu, C. G., Sabatino, G., Negrini, M., Maira, G., Croce, C. M., and Farace, M. G. (2005) Extensive modulation of a set of microRNAs in primary glioblastoma, Biochemical and Biophysical Research Communications 334, 1351–1358.
Iorio, M. V., Ferracin, M., Liu, C. G., Veronese, A., Spizzo, R., Sabbioni, S., Magri, E., Pedriali, M., Fabbri, M., Campiglio, M., Menard, S., Palazzo, J. P., Rosenberg, A., Musiani, P., Volinia, S., Nenci, I., Calin, G. A., Querzoli, P., Negrini, M., and Croce, C. M. (2005) MicroRNA gene expression deregulation in human breast cancer, Cancer Research 65, 7065–7070.
Szafranska, A. E., Davison, T. S., John, J., Cannon, T., Sipos, B., Maghnouj, A., Labourier, E., and Hahn, S. A. (2007) MicroRNA expression alterations are linked to tumorigenesis and non-neoplastic processes in pancreatic ductal adenocarcinoma, Oncogene 26, 4442–4452.
Varnholt, H., Drebber, U., Schulze, F., Wedemeyer, I., Schirmacher, P., Dienes, H. P., and Odenthal, M. (2008) MicroRNA gene expression profile of hepatitis C virus-associated hepatocellular carcinoma, Hepatology 47, 1223–1232.
Yanaihara, N., Caplen, N., Bowman, E., Seike, M., Kumamoto, K., Yi, M., Stephens, R. M., Okamoto, A., Yokota, J., Tanaka, T., Calin, G. A., Liu, C. G., Croce, C. M., and Harris, C. C. (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis, Cancer Cell 9, 189–198.
Gusev, Y., Schmittgen, T. D., Lerner, M., Postier, R., and Brackett, D. (2007) Computational analysis of biological functions and pathways collectively targeted by co-expressed microRNAs in cancer, BMC Bioinformatics 8 Suppl 7, S16.
Lewis, B. P., Burge, C. B., and Bartel, D. P. (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets, Cell 120, 15–20.
Grimson, A., Farh, K. K., Johnston, W. K., Garrett-Engele, P., Lim, L. P., and Bartel, D. P. (2007) MicroRNA targeting specificity in mammals: determinants beyond seed pairing, Molecular Cell 27, 91–105.
Wang, Y. P., and Li, K. B. (2009) Correlation of expression profiles between microRNAs and mRNA targets using NCI-60 data, BMC Genomics 10, 218.
Selbach, M., Schwanhausser, B., Thierfelder, N., Fang, Z., Khanin, R., and Rajewsky, N. (2008) Widespread changes in protein synthesis induced by microRNAs, Nature 455, 58–63.
Baek, D., Villen, J., Shin, C., Camargo, F. D., Gygi, S. P., and Bartel, D. P. (2008) The impact of microRNAs on protein output, Nature 455, 64–71.
Liu, Q., Fu, H., Sun, F., Zhang, H., Tie, Y., Zhu, J., **ng, R., Sun, Z., and Zheng, X. (2008) miR-16 family induces cell cycle arrest by regulating multiple cell cycle genes, Nucleic Acids Research 36, 5391–5404.
Cloonan, N., Brown, M. K., Steptoe, A. L., Wani, S., Chan, W. L., Forrest, A. R., Kolle, G., Gabrielli, B., and Grimmond, S. M. (2008) The miR-17-5p microRNA is a key regulator of the G1/S phase cell cycle transition, Genome Biology 9, R127.
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Chen, SJ., Chen, HC. (2011). Analysis of Targets and Functions Coregulated by MicroRNAs. 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_16
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DOI: https://doi.org/10.1007/978-1-60761-863-8_16
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