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.

  • Comment
  • Published:

Novel approaches toward managing the micromanagers: ‘non-toxic’ but effective

Gene Therapy volume 23, pages 697–698 (2016)Cite this article

Subjects

Many common diseases that plague our civilized society, such as heart disease, cancer, metabolic and inflammatory disease are of complex nature and involve the dysregulation of multiple genes at any given time. In a world of increasingly complex disease etiologies, microRNAs are rapidly gaining recognition as either the root cause of certain diseases, as a novel diagnostic tool or as an essential therapeutic target. MiRNAs are small, non-coding RNAs that are highly conserved among species and contribute to more than 4% of all human genes.1, 2 Most miRNAs have only weak effects on gene expression, allowing for precise expression control and reduction of expression noise.3, 4, 5 The ability of miRNAs to fine-tune mRNA expression profiles during cellular differentiation, evolution and development, and at the crucial balance between cancer cell apoptosis and proliferation has prompted a comparison with a rheostat and resulted in the nickname ‘micromanagers of gene expression’.6, 7 Current knowledge indicates that the expression of thousands of mRNAs in each cell type is controlled by ‘armies of miRNA micromanagers’, and that during the diseases mentioned above these micromanagers are somewhat out of control.

There are a number of reasons for the emerging focus on microRNAs as key regulators of complex disease pathologies such as the role of miR-155 in inflammatory diseases and hematopoiesis, the involvement of miR-33 and miR-103/107 in metabolic disease and the contributions of miR-15 family miRNAs in certain cancers and cardiac regeneration.8 MicroRNAs frequently regulate multiple genes or functionally related genes because they only need to be partially complementary to their target mRNAs, a phenomenon called imperfect base pairing.9 Examples of miRNAs regulating sets of genes include miR-29 as a key extracellular matrix remodeling miRNA10, 11 and miR-138 as a periodontal homeostasis regulator.12 The ability of miRNA clusters to target sets of related genes is especially significant as it has been demonstrated that human monogenic disease genes frequently have functionally redundant paralogues.13

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

Relevant articles

Open Access articles citing this article.

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

References

  1. Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP . The impact of microRNAs on protein output. Nature 2008; 455: 64–71.

    Article  CAS  Google Scholar 

  2. Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N . Widespread changes in protein synthesis induced by microRNAs. Nature 2008; 455: 58–63.

    Article  CAS  Google Scholar 

  3. Ambros V . MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 2003; 113: 673–676.

    Article  CAS  Google Scholar 

  4. Bartel DP . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281–297.

    Article  CAS  Google Scholar 

  5. Schmiedel JM, Klemm SL, Zheng Y, Sahay A, Blüthgen N, Marks DS et al. Gene expression. MicroRNA control of protein expression noise. Science 2015; 348: 128–132.

    Article  CAS  Google Scholar 

  6. Bartel DP, Chen CZ . Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat Rev Genet 2004; 5: 396–400.

    Article  CAS  Google Scholar 

  7. Sevignani C, Calin GA, Siracusa LD, Croce CM . Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome 2006; 17: 189–202.

    Article  CAS  Google Scholar 

  8. van Rooij E, Purcell AL, Levin AA . Developing microRNA therapeutics. Circ Res 2012; 110: 496–507.

    Article  CAS  Google Scholar 

  9. Lam JK, Chow MY, Zhang Y, Leung SW . siRNA Versus miRNA as Therapeutics for Gene Silencing. Mol Ther Nucleic Acids 2015; 4: e252.

    Article  CAS  Google Scholar 

  10. Altuvia Y, Landgraf P, Lithwick G, Elefant N, Pfeffer S, Aravin A et al. Clustering and conservation patterns of human microRNAs. Nucleic Acids Res 2005; 33: 2697–2706.

    Article  CAS  Google Scholar 

  11. Chen Y, Mohammed A, Oubaidin M, Evans CA, Zhou X, Luan X et al. Cyclic stretch and compression forces alter microRNA-29 expression of human periodontal ligament cells. Gene 2015; 566: 13–17.

    Article  CAS  Google Scholar 

  12. Zhou X, Luan X, Chen Z, Francis M, Gopinathan G, Li W et al. MicroRNA-138 inhibits periodontal progenitor differentiation under inflammatory conditions. J Dent Res 2016; 95: 230–237.

    Article  Google Scholar 

  13. Chen WH, Zhao XM, van Noort V, Bork P . Human monogenic disease genes have frequently functionally redundant paralogs. PLoS Comput Biol 2013; 9: e1003073.

    Article  CAS  Google Scholar 

  14. Almeida MI, Reis RM, Calin GA . MicroRNA history: discovery, recent applications, and next frontiers. Mutat Res 2011; 717: 1–8.

    Article  CAS  Google Scholar 

  15. Sundarbose K, Kartha RV, Subramanian S MicroRNAs as biomarkers in cancer Diagnostics (Basel) 2013; 3: 84–104.

    Article  CAS  Google Scholar 

  16. Etheridge A, Lee I, Hood L, Galas D, Wang K . Extracellular microRNA: a new source of biomarkers. Mutat Res 2011; 717: 85–90.

    Article  CAS  Google Scholar 

  17. Wang J, Chen J, Sen S . MicroRNA as biomarkers and diagnostics. J Cell Physiol 2016; 231: 25–30.

    Article  CAS  Google Scholar 

  18. van Rooij E, Sutherland LB, Qi X, Richardson JA, Hill J, Olson EN . Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007; 316: 575–579.

    Article  CAS  Google Scholar 

  19. Deng Y, Ai J, Guan X, Wang Z, Yan B, Zhang D et al. MicroRNA and messenger RNA profiling reveals new biomarkers and mechanisms for RDX induced neurotoxicity. BMC Genomics 2014; 15 (Suppl 11): S1.

    Article  Google Scholar 

  20. Cao H, Yu W, Li X, Wang J, Gao S, Holton NE et al. A new plasmid-based microRNA inhibitor system that inhibits microRNA families in transgenic mice and cells: a potential new therapeutic reagent. Gene Ther 2016; 23: 527–542.

    Article  CAS  Google Scholar 

  21. Villarreal G Jr, Oh DJ, Kang MH, Rhee DJ . Coordinated regulation of extracellular matrix synthesis by the microRNA-29 family in the trabecular meshwork. Invest Ophthalmol Vis Sci 2011; 52: 3391–3397.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, TX, USA

    T G H Diekwisch

Authors
  1. T G H Diekwisch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T G H Diekwisch.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Diekwisch, T. Novel approaches toward managing the micromanagers: ‘non-toxic’ but effective. Gene Ther 23, 697–698 (2016). https://doi.org/10.1038/gt.2016.49

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gt.2016.49

This article is cited by

Search

Advanced search

Quick links