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Computational Systems Biology Approach Predicts Regulators and Targets of microRNAs and Their Genomic Hotspots in Apoptosis Process

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Abstract

Novel computational systems biology tools such as common targets analysis, common regulators analysis, pathway discovery, and transcriptomic-based hotspot discovery provide new opportunities in understanding of apoptosis molecular mechanisms. In this study, after measuring the global contribution of microRNAs in the course of apoptosis by Affymetrix platform, systems biology tools were utilized to obtain a comprehensive view on the role of microRNAs in apoptosis process. Network analysis and pathway discovery highlighted the crosstalk between transcription factors and microRNAs in apoptosis. Within the transcription factors, PRDM1 showed the highest upregulation during the course of apoptosis, with more than 9-fold expression increase compared to non-apoptotic condition. Within the microRNAs, MIR1208 showed the highest expression in non-apoptotic condition and downregulated by more than 6 fold during apoptosis. Common regulators algorithm showed that TNF receptor is the key upstream regulator with a high number of regulatory interactions with the differentially expressed microRNAs. BCL2 and AKT1 were the key downstream targets of differentially expressed microRNAs. Enrichment analysis of the genomic locations of differentially expressed microRNAs led us to the discovery of chromosome bands which were highly enriched (p < 0.01) with the apoptosis-related microRNAs, such as 13q31.3, 19p13.13, and Xq27.3 This study opens a new avenue in understanding regulatory mechanisms and downstream functions in the course of apoptosis as well as distinguishing genomic-enriched hotspots for apoptosis process.

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Acknowledgments

Computational analysis of this research was supported by School of Biological Sciences Science of The University of Adelaide.

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    Authors and Affiliations

    1. National Center of Biotechnology (NCB), King Abdulaziz City for Science and Technology (KACST), Riyadh, 6086, Saudi Arabia

      Ibrahim O. Alanazi

    2. School of Biological Sciences, The University of Adelaide, Adelaide, SA, 5005, Australia

      Ibrahim O. Alanazi & Esmaeil Ebrahimie

    3. Institute of Biotechnology, Shiraz University, Shiraz, Iran

      Esmaeil Ebrahimie

    4. Division of Information Technology, Engineering and the Environment, School of Information Technology and Mathematical Sciences, University of South Australia, Adelaide, Australia

      Esmaeil Ebrahimie

    5. School of Biological Sciences, Faculty of Science and Engineering, Flinders University, Adelaide, Australia

      Esmaeil Ebrahimie

    6. Department of Genetics and Evolution, School of Biological Sciences, North Terrace Campus, The University of Adelaide, Adelaide, SA, 5005, Australia

      Esmaeil Ebrahimie

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    1. Ibrahim O. Alanazi
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    Correspondence to Ibrahim O. Alanazi or Esmaeil Ebrahimie.

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    Ibrahim Alanazi and Esmaeil Ebrahimie have been contributed equally to this work.

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    Alanazi, I.O., Ebrahimie, E. Computational Systems Biology Approach Predicts Regulators and Targets of microRNAs and Their Genomic Hotspots in Apoptosis Process. Mol Biotechnol 58, 460–479 (2016). https://doi.org/10.1007/s12033-016-9938-x

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