Skip to main content

Analysis of Targets and Functions Coregulated by MicroRNAs

  • Protocol
  • First Online:
MicroRNA and Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 676))

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ambros, V. (2004) The functions of animal microRNAs, Nature 431, 350–355.

    Article  PubMed  CAS  Google Scholar 

  2. Bartel, D. P. (2004) MicroRNAs: genomics, biogenesis, mechanism, and function, Cell 116, 281–297.

    Article  PubMed  CAS  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. Chen, C. Z. (2005) MicroRNAs as oncogenes and tumor suppressors, New England Journal of Medicine 353, 1768–1771.

    Article  PubMed  CAS  Google Scholar 

  6. Croce, C. M. (2008) Oncogenes and cancer, New England Journal of Medicine 358, 502–511.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    Article  PubMed  CAS  Google Scholar 

  9. 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.

    Article  PubMed  CAS  Google Scholar 

  10. 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.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    Article  PubMed  CAS  Google Scholar 

  15. 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.

    Article  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  CAS  Google Scholar 

  17. 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.

    Article  PubMed  CAS  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

  20. 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.

    Article  PubMed  CAS  Google Scholar 

  21. Liu, Q., Fu, H., Sun, F., Zhang, H., Tie, Y., Zhu, J., Xing, 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.

    Article  PubMed  CAS  Google Scholar 

  22. 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.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

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

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-863-8_16

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-862-1

  • Online ISBN: 978-1-60761-863-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics