Skip to main content

Roles of MicroRNAs in Cancers and Development

  • Protocol
  • First Online:
RNA Interference

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1218))

Abstract

MicroRNAs (miRNAs) are small noncoding RNA molecules thought to play an important role in regulating gene expression. Although knowledge of the biological functions of most miRNAs is still limited, miRNAs are thought to regulate the gene expression in various diseases and embryo development. In this chapter, the roles of miRNAs in human cancers are first examined from the viewpoint of up- and downregulation. Oncogenic miRNAs are involved in the overexpression/upregulation of cancers, whereas suppressive miRNAs are involved in the underexpression/downregulation of cancers. Statistical analysis of the positional nucleotide occurrence features of miRNAs revealed differences between the positional nucleotide occurrences of oncogenic and suppressive miRNAs. A miRNA gene-silencing score was then defined on the basis of the higher and lower levels of the statistical significances of positional nucleotides. Since the miRNA scores were closely related to miRNA frequencies, a method using the scores and nucleotide frequencies to distinguish whether a new miRNA is oncogenic or suppressive is proposed. This chapter also describes the roles of miRNAs in development. As miRNAs can act as cis-regulatory elements in the early embryonic development of Drosophila melanogaster, it is proposed that they mediate signal transduction between genes.

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 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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. Aravin A, Logos-Quintana M, Yalcin A, Zavolan M, Marks D, Snyder B, Gaasterland T, Meyer J, Tuschl T (2003) The small RNA profile during Drosophila melanogaster development. Dev Cell 5:337–350

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  3. Doench JG, Sharp PA (2004) Specificity of microRNA target selection in translational repression. Genes Dev 18:504–511

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  4. Lai EC (2002) Micro RNAs are complementary to 3’ UTR sequence motifs that mediate negative post-transcriptional regulation. Nat Genet 30:363–364

    Article  PubMed  CAS  Google Scholar 

  5. Volinia S, Calin GA, Liu CG et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A 103:2257–2261

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  6. Chan JA, Krichevsky AM, Kosik KS (2005) MicroRNA-21 is an antiapoptotic factor inhuman glioblastoma cells. Cancer Res 65:6029–6033

    Article  PubMed  CAS  Google Scholar 

  7. Takeshita F, Mina Y, Nagahara S et al (2005) Efficient delivery of small interfering RNA to bone-metastatic tumors by using atelocollagen in vivo. Proc Natl Acad Sci U S A 102:12177–12182

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Calin GA, Ferracin M, Cimmino A et al (2005) A microRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Eng J Med 353:1793–1801

    Article  CAS  Google Scholar 

  9. Saito Y, Liang G, Egger G et al (2006) Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL-6 by chromatin-modifying drugs in human cancer cells. Cancer Cell 9:435–443

    Article  PubMed  CAS  Google Scholar 

  10. Takamizawa J, Konishi H, Yanagisawa K et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756

    Article  PubMed  CAS  Google Scholar 

  11. Zhang HH, Wang XJ, Li GX et al (2007) Deletion of let-7a microRNA by real time PCR in gastric carcinoma. World J Gastroenterol 13:2883–2888

    PubMed  CAS  Google Scholar 

  12. Yanaihara N, Caplen N, Bowman E et al (2006) Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 9:189–198

    Article  PubMed  CAS  Google Scholar 

  13. Feber A, Xi L, Luketich JD et al (2008) MicroRNA expression profiles of esophageal cancer. J Thoracic Cardiovasc Surg 135:255–260

    Article  CAS  Google Scholar 

  14. Bandres E, Cubedo E, Agirre X et al (2006) Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer 5:29

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Gramantieri L, Ferracin M, Fornari F et al (2007) Cyclin G1 is a target of miR-122a, a microRNA frequency down-regulated in human hepatocellular carcinoma. Cancer Res 67:6092–6099

    Article  PubMed  CAS  Google Scholar 

  16. Michael MZ, O’Conner SM, van Holst Pellekaan NG et al (2003) Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1:882–891

    PubMed  CAS  Google Scholar 

  17. Meng F, Henson R, Wehbe-Janek H et al (2007) MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133:647–658

    Article  PubMed  CAS  Google Scholar 

  18. Murakami Y, Yasuda T, Saigo K et al (2006) Comprehensive analysis of microRNA expression patterns in hepatocellular carcinoma and non-tumorous tissues. Oncogene 25:2537–2545

    Article  PubMed  CAS  Google Scholar 

  19. Esquela-kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269

    Article  PubMed  CAS  Google Scholar 

  20. Lui WO, Pourmand N, Patterson BK, Fire A (2007) Patterns of known and novel small RNAs in human cervical cancer. Cancer Res 67:6031–6043

    Article  PubMed  CAS  Google Scholar 

  21. Akao Y, Nakagawa Y, Kitade Y et al (2007) Downregulation of microRNAs-143 and -145 in B-cell malignancies. Cancer Sci 98:1914–1920

    Article  PubMed  CAS  Google Scholar 

  22. Calin GA, Dumitru CD, Shimizu M et al (2002) Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99:15524–15529

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  PubMed  CAS  Google Scholar 

  24. Calin GA, Sevignani C, Dumitru CD et al (2004) Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A 101:2999–3004

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Calin CA, Liu CG, Sevignani C et al (2004) MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci U S A 101:11755–11760

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Osaki M, Takeshita F, Ochiya T (2008) MicroRNAs as biomarkers and therapeutic drugs in human cancer. Biomarkers 13:658–670

    Article  PubMed  CAS  Google Scholar 

  27. Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A, Enright AJ (2006) miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34:D140–D144

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Kozomara A, Griffiths-Jones S (2010) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res 39:D152–D157

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854

    Article  PubMed  CAS  Google Scholar 

  30. Wightman B, Ha I, Ruvkun G (1993) Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75:855–862

    Article  PubMed  CAS  Google Scholar 

  31. Enright AJ, John B, Gaul U, Tuschl T, Sander C, Marks DS (2003) MicroRNA targets in Drosophila. Genome Biol 5:R1

    Article  PubMed  PubMed Central  Google Scholar 

  32. Stark A, Brennecke J, Russell RB, Cohen SM (2003) Identification of Drosophila microRNA targets. PLoS Biol 1:E60

    Article  PubMed  PubMed Central  Google Scholar 

  33. Gesellchen V, Broutros M (2004) Managing the genome: microRNAs in Drosophila. Differentiation 72:74–84

    Article  PubMed  Google Scholar 

  34. Biemar F, Zinzen R, Ronshaugen M, Sementchenko V, Manak JR, Levine MS (2005) Spatial regulation of microRNA gene expression in the Drosophila embryo. Proc Natl Acad Sci U S A 102:15907–15911

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Aboobaker AA, Tomancak P, Patel N, Rubin GM, Lai EC (2005) Drosophila microRNAs exhibit diverse spatial expression patterns during embryonic development. Proc Natl Acad Sci U S A 102:18017–18022

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  36. Bentwich I (2005) Prediction and validation of microRNAs and their targets. FEBS Lett 579:5904–5910

    Article  PubMed  CAS  Google Scholar 

  37. Wienholds E, Plasterk RHA (2005) MicroRNA function in animal development. FEBS Lett 579:5911–5922

    Article  PubMed  CAS  Google Scholar 

  38. Robins H, Li Y, Padgett RW (2005) Incorporating structure to predict microRNA targets. Proc Natl Acad Sci U S A 102:4006–4009

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. Lai EC, Tam B, Rubin GM (2005) Pervasive regulation of Drosophila Notch target genes by Gy-box-, Brd-box-, and K-box-class microRNAs. Genes Dev 19:1067–1080

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  41. Carthew RW, Sontheimer EJ (2009) Origins and mechanisms of miRNAs and siRNAs. Cell 136:642–655

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  42. Driever W, Nusselein-Volhard C (1989) The bicoid protein is a positive regulator of hunchback transcription in the early Drosophila embryo. Nature 337:138–143

    Article  PubMed  CAS  Google Scholar 

  43. Driever W, Thoma G, Nusselein-Volhard C (1989) Determination of spatial domains of zygotic gene expression in the Drosophila embryo by the affinity of binding sites for the bicoid morphogen. Nature 340:363–367

    Article  PubMed  CAS  Google Scholar 

  44. Struhl G, Struhl K, Macdonald PM (1989) The gradient morphogen bicoid is a concentration-dependent transcriptional activator. Cell 57:1259–1273

    Article  PubMed  CAS  Google Scholar 

  45. Hanes SD, Brent R (1991) A genetic model for interaction of the homeodomain recognition helix with DNA. Science 251:427–430

    Article  Google Scholar 

  46. St Johnston D, Nusselein-Volhard C (1992) The origin of pattern and polarity in the Drosophila embryo. Cell 68:201–219

    Article  PubMed  CAS  Google Scholar 

  47. Small S, Blair R, Levine M (1992) Regulation of even-skipped stripe 2 in the Drosophila embryo. EMBO J 11:4047–4057

    PubMed  CAS  PubMed Central  Google Scholar 

  48. Burz DS, Rivera-Pomar R, Jackle H, Hanes SD (1998) Cooperative DNA-binding by Bicoid provides a mechanism for threshold-dependent gene activation in the Drosophila embryo. EMBO J 17:5998–5999

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  49. Crauk O, Dostatni N (2005) Bicoid determines sharp and precise target gene expression in the Drosophila embryo. Curr Biol 15:1888–1898

    Article  PubMed  CAS  Google Scholar 

  50. Xie X, Lu J, Kulbokas EJ, Golub TR, Mootha V, Lindblad-Toh K, Lander ES, Lellis M (2005) Systematic discovery of regulatory motifs in human promoters and 3’ UTRs by comparison of several mammals. Nature 434:338–345

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  51. Hobert O (2004) Common logic of transcription factor and microRNA action. Trends Biochem Sci 29:462–468

    Article  PubMed  CAS  Google Scholar 

  52. Helden J (2003) Regulatory sequence analysis tools. Nucleic Acids Res 31:3593–3596

    Article  PubMed  PubMed Central  Google Scholar 

  53. Bergman CM, Carlson JW, Celniker SE (2005) Drosophila DNase I footprint database: a systematic genome annotation of transcription factor binding sites in the fruit fly, Drosophila melanogaster. Bioinfomatics 21:1747–1749

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shigeru Takasaki .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this protocol

Cite this protocol

Takasaki, S. (2015). Roles of MicroRNAs in Cancers and Development. In: Sioud, M. (eds) RNA Interference. Methods in Molecular Biology, vol 1218. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1538-5_24

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-1538-5_24

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-1537-8

  • Online ISBN: 978-1-4939-1538-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics