Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Progress
  • Published:

microRNAs join the p53 network — another piece in the tumour-suppression puzzle

Nature Reviews Cancer volume 7, pages 819–822 (2007)Cite this article

Abstract

Several recent studies have found a conserved microRNA (miRNA) family, the miR-34s, to be direct transcriptional targets of p53. miR-34 activation can recapitulate elements of p53 activity, including induction of cell-cycle arrest and promotion of apoptosis, and loss of miR-34 can impair p53-mediated cell death. These data reinforce the growing awareness that non-coding RNAs are key players in tumour development by placing miRNAs in a central role in a well-known tumour-suppressor network.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Current model of miRNA biogenesis and post-transcriptional silencing.
Figure 2: A model of the p53–miR-34 network in regulating cell proliferation and cell death.

Similar content being viewed by others

References

  1. Lowe, S. W., Cepero, E. & Evan, G. Intrinsic tumour suppression. Nature 432, 307–315 (2004).

    Article  CAS  Google Scholar 

  2. Vogelstein, B. B., Lane, D. D. & Levine, A. A. J. Surfing the p53 network. Nature 408, 307–310 (2000).

    CAS  Google Scholar 

  3. Bommer, G. T. et al. p53-mediated activation of miRNA34 candidate tumor-suppressor genes. Curr. Biol. 17, 1298–1307 (2007).

    Article  CAS  Google Scholar 

  4. Chang, T. C. et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol. Cell 26, 745–752 (2007).

    Article  CAS  Google Scholar 

  5. He, L. et al. A microRNA component of the p53 tumour suppressor network. Nature 447, 1130–1134 (2007).

    Article  CAS  Google Scholar 

  6. Raver-Shapira, N. et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol. Cell 26, 731–743 (2007).

    Article  CAS  Google Scholar 

  7. Tarasov, V. et al. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle 6, 1586–1593 (2007).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Zamore, P. D. & Haley, B. Ribo-gnome: the big world of small RNAs. Science 309, 1519–1524 (2005).

    Article  CAS  Google Scholar 

  10. Doench, J. G. & Sharp, P. A. Specificity of microRNA target selection in translational repression. Genes Dev. 18, 504–511 (2004).

    Article  CAS  Google Scholar 

  11. Bhattacharyya, S. N., Habermacher, R., Martine, U., Closs, E. I. & Filipowicz, W. Stress-induced reversal of microRNA repression and mRNA P-body localization in human cells. Cold Spring Harb. Symp. Quant. Biol. 71, 513–521 (2006).

    Article  CAS  Google Scholar 

  12. Iorio, M. V. et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65, 7065–7070 (2005).

    Article  CAS  Google Scholar 

  13. Volinia, S. et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl Acad. Sci. USA 103, 2257–2261 (2006).

    Article  CAS  Google Scholar 

  14. Akao, Y., Nakagawa, Y. & Naoe, T. MicroRNAs 143 and 145 are possible common onco-microRNAs in human cancers. Oncol. Rep. 16, 845–850 (2006).

    CAS  PubMed  Google Scholar 

  15. Calin, G. A. et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc. Natl Acad. Sci. USA 101, 2999–3004 (2004).

    Article  CAS  Google Scholar 

  16. Dews, M. et al. Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster. Nature Genet. 38, 1060–1065 (2006).

    Article  CAS  Google Scholar 

  17. He, L. et al. A microRNA polycistron as a potential human oncogene. Nature 435, 828–833 (2005).

    Article  CAS  Google Scholar 

  18. O'Donnell, K. A., Wentzel, E. A., Zeller, K. I., Dang, C. V. & Mendell, J. T. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839–843 (2005).

    Article  CAS  Google Scholar 

  19. Voorhoeve, P. M. et al. A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124, 1169–1181 (2006).

    Article  CAS  Google Scholar 

  20. Tam, W. & Dahlberg, J. E. miR-155/BIC as an oncogenic microRNA. Genes Chromosomes Cancer 45, 211–212 (2006).

    Article  CAS  Google Scholar 

  21. Calin, G. A. et al. Frequent deletions and down-regulation of micro- RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc. Natl Acad. Sci. USA 99, 15524–15529 (2002).

    Article  CAS  Google Scholar 

  22. Johnson, S. M. et al. RAS is regulated by the let-7 microRNA family. Cell 120, 635–647 (2005).

    Article  CAS  Google Scholar 

  23. Mayr, C., Hemann, M. T. & Bartel, D. P. Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation. Science 315, 1576–1579 (2007).

    Article  CAS  Google Scholar 

  24. Lu, J. et al. MicroRNA expression profiles classify human cancers. Nature 435, 834–838 (2005).

    Article  CAS  Google Scholar 

  25. Thomson, J. M. et al. Extensive post-transcriptional regulation of microRNAs and its implications for cancer. Genes Dev. 20, 2202–2207 (2006).

    Article  CAS  Google Scholar 

  26. Kumar, M. S., Lu, J., Mercer, K. L., Golub, T. R. & Jacks, T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nature Genet. 39, 673–677 (2007).

    Article  CAS  Google Scholar 

  27. Yu, J. J. et al. Identification and classification of p53-regulated genes. Proc. Natl Acad. Sci. USA 96, 14517–14522 (1999).

    Article  CAS  Google Scholar 

  28. Zhao, R. R. et al. Analysis of p53-regulated gene expression patterns using oligonucleotide arrays. Genes Dev. 14, 981–993 (2000).

    Article  CAS  Google Scholar 

  29. Brugarolas, J. et al. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377, 552–557 (1995).

    Article  CAS  Google Scholar 

  30. Wei, C. L. et al. A global map of p53 transcription-factor binding sites in the human genome. Cell 124, 207–219 (2006).

    Article  CAS  Google Scholar 

  31. Lewis, B. P., Burge, C. B. & Bartel, D. P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15–20 (2005).

    Article  CAS  Google Scholar 

  32. Spurgers, K. B. et al. Identification of cell cycle regulatory genes as principal targets of p53-mediated transcriptional repression. J. Biol. Chem. 281, 25134–25142 (2006).

    Article  CAS  Google Scholar 

  33. Lee, R. C., Feinbaum, R. L. & Ambros, V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854 (1993).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  35. Versteeg, R. et al. 1p36: every subband a suppressor? Eur. J. Cancer 31A, 538–541 (1995).

    Article  CAS  Google Scholar 

  36. Bagchi, A. et al. CHD5 is a tumor suppressor at human 1p36. Cell 128, 459–475 (2007).

    Article  CAS  Google Scholar 

  37. Welch, C., Chen, Y. & Stallings, R. L. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene 26, 5017–5022 (2007).

    Article  CAS  Google Scholar 

  38. Gaur, A. et al. Characterization of microRNA expression levels and their biological correlates in human cancer cell lines. Cancer Res. 67, 2456–2468 (2007).

    Article  CAS  Google Scholar 

  39. Xi, Y., Shalgi, R., Fodstad, O., Pilpel, Y. & Ju, J. Differentially regulated micro-RNAs and actively translated messenger RNA transcripts by tumor suppressor p53 in colon cancer. Clin. Cancer Res. 12, 2014–2024 (2006).

    Article  CAS  Google Scholar 

  40. Lau, N. C., Lim, L. P., Weinstein, E. G. & Bartel, D. P. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294, 858–862 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

I.H. is supported by a K99 grant from the US National Institutes of Health (NIH). X.H. is supported by a predoctoral fellowship from the DOB Breast Cancer Research Program. This work was supported in part by grants from the NIH (S.W.L. and G.J.H.) and a kind gift from Kathryn W. Davis (G.J.H.).

Author information

Authors and Affiliations

  1. Lin He, Xingyue He, Scott W. Lowe and Gregory J. Hannon are at the Watson School of Biological Sciences, Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.,

    Lin He, Xingyue He, Scott W. Lowe & Gregory J. Hannon

  2. Xingyue He is at the Program in Genetics, Stony Brook University, Stony Brook, New York 11794, USA.,

    Xingyue He

Authors
  1. Lin He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xingyue He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Scott W. Lowe
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gregory J. Hannon
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregory J. Hannon.

Related links

Related links

FURTHER INFORMATION

Scott Lowe's website

Greg Hannon's website

Rights and permissions

Reprints and permissions

About this article

Cite this article

He, L., He, X., Lowe, S. et al. microRNAs join the p53 network — another piece in the tumour-suppression puzzle. Nat Rev Cancer 7, 819–822 (2007). https://doi.org/10.1038/nrc2232

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc2232

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing