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Identifying transcription factor and microRNA mediated synergetic regulatory networks in lung cancer

Background

It has been demonstrated that, at the network level, the transcriptional regulation by transcription factors (TFs) and post-transcriptional regulation by microRNAs (miRNAs) are tightly coupled. Aberrant expression of these bio-molecules is linked to several diseases, including lung cancer. In this study, we pursued a regulatory network-based approach mediated by TFs and miRNAs for a comprehensive investigation of gene regulation patterns in lung cancer.

Materials and methods

We introduced a directional network that corresponds to significantly differentially expressed (DE) miRNAs and genes between lung tumor and matched normal samples. We predicted miRNA targets in genes by parsing TargetScan prediction results. To find the regulation of TF to genes or miRNAs, we explored the TFs and their binding profiles from the TRANSFAC Professional database. TFs are either significantly DE or have target molecules which are significantly enriched in DE subspace. In this approach, a signed edge of the network illustrates potential repression or activation/repression mediated by a miRNA or TF, respectively, to their target molecules.

Results and conclusions

We obtained a significantly enriched set of TF- miRNA mediated three-node based feed forward loops (FFLs) with signed edges. The edges of the signed three-node FFLs were validated using completely independent data set. The observation of critical miRNAs in the Wnt signaling pathway, with partial verification from previous studies, demonstrates that our network-based approach is promising for the identification of new and important miRNAs and their regulation in lung cancer.

Acknowledgements

We would like to thank the members in Bioinformatics and Systems Medicine Laboratory for their valuable discussion in this project. This work was partially supported by National Institutes of Health grants (R01LM011177, P30CA68485, and P50CA095103).

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Correspondence to Zhongming Zhao.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( https://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.

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Mitra, R., Sun, J., Zhao, M. et al. Identifying transcription factor and microRNA mediated synergetic regulatory networks in lung cancer. BMC Bioinformatics 14, A14 (2013). https://doi.org/10.1186/1471-2105-14-S17-A14

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Keywords

  • Lung Cancer
  • miRNA Target
  • Differentially Express
  • Directional Network
  • Feed Forward Loop