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.

  • Short Communication
  • Published:

Selection of optimal combinations of target genes for therapeutic multi-gene silencing based on miRNA co-regulation

Abstract

Therapeutic gene silencing is a promising approach for treatment of cancer. Despite substantial efforts, however, only few such therapeutic methods have been clinically tested. The heterogeneity in gene expression profiles among malignant tissues and the dynamic control of gene expression in individual tumors makes identifying universal and effective targets a challenge. Further development of gene silencing therapy requires new approaches to comprehend and manage gene expression in cancer cells. In this study, we proposed and evaluated experimentally a new approach to design multi-gene silencing therapy. Using a simplified model of gene expression control, we show that genes commonly regulated by the same microRNA represent optimal combinations of targets for small hairpin RNA/small interfering RNA-based gene silencing. The proposed method of target gene selection and co-silencing can be explored as an algorithm for personalized cancer gene therapy.

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

Access options

Buy this article

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

Figure 1

Similar content being viewed by others

References

  1. Rodon J, Perez J, Kurzrock R . Combining targeted therapies: practical issues to consider at the bench and bedside. Oncologist 2010; 15: 37–50.

    Article  PubMed Central  Google Scholar 

  2. Li C, Zhang X, Cheng L, Dai L, Xu F, Zhang J et al. RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice. Cancer Gene Ther 2013; 20: 101–108.

    Article  Google Scholar 

  3. Shahzad MM, Lu C, Lee JW, Stone RL, Mitra R, Mangala LS et al. Dual targeting of EphA2 and FAK in ovarian carcinoma. Cancer Biol Ther 2009; 8: 1027–1034.

    Article  CAS  PubMed Central  Google Scholar 

  4. Punt CJ, Tol J . More is less -- combining targeted therapies in metastatic colorectal cancer. Nat Rev Clin Oncol 2009; 6: 731–733.

    Article  CAS  PubMed Central  Google Scholar 

  5. Bhardwaj N, Yan KK, Gerstein MB . Analysis of diverse regulatory networks in a hierarchical context shows consistent tendencies for collaboration in the middle levels. Proc Natl Acad Sci USA 2010; 107: 6841–6846.

    Article  CAS  Google Scholar 

  6. Malek A, Bakhidze E, Noske A, Sers C, Aigner A, Schäfer R et al. HMGA2 gene is a promising target for ovarian cancer silencing therapy. Int J Cancer 2008; 123: 348–356.

    Article  CAS  Google Scholar 

  7. Malek A, Schafer R, Tchernitsa O . Target genes suitable for silencing approaches and protein product interference in ovarian epithelial cancer. Cancer Treat Rev 2010; 36: 8–15.

    Article  CAS  Google Scholar 

  8. Zhang S, Li Q, Liu J, Zhou XJ . A novel computational framework for simultaneous integration of multiple types of genomic data to identify microRNA-gene regulatory modules. Bioinformatics 2011; 27: i401–i409.

    Article  CAS  PubMed Central  Google Scholar 

  9. Zhdanov VP . Kinetic models of gene expression including non-coding RNAs. Physics Reports 2011; 500: 1–42.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A Malek.

Ethics declarations

Competing interests

The authors declare no conflict of interest

Additional information

Supplementary Information accompanies the paper on Cancer Gene Therapy website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Malek, A., Gyorffy, B., Catapano, C. et al. Selection of optimal combinations of target genes for therapeutic multi-gene silencing based on miRNA co-regulation. Cancer Gene Ther 20, 326–329 (2013). https://doi.org/10.1038/cgt.2013.20

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cgt.2013.20

Keywords

Search

Quick links