A mathematical model as a tool to identify microRNAs with highest impact on transcriptome changes

BMC Genomics

Krzysztof Biernacki¹  Krzysztof Fujarewicz²  Marzena Mura²  Marek Kimmel²  Anna Lalik²  Roman Jaksik²  Joanna Rzeszowska-Wolny² 

[1] Department of Medical and Molecular Biology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia in Katowice;Department of Systems Engineering, Institute of Automatic Control, Silesian University of Technology;

关键词: miRNA;    miRNA-mRNA interactions;    ionizing radiation;    stressing factor;   

DOI  :  10.1186/s12864-019-5464-0

来源: DOAJ

【 摘 要 】

Abstract Background Rapid changes in the expression of many messenger RNA (mRNA) species follow exposure of cells to ionizing radiation. One of the hypothetical mechanisms of this response may include microRNA (miRNA) regulation, since the amounts of miRNAs in cells also vary upon irradiation. To address this possibility, we designed experiments using cancer-derived cell lines transfected with luciferase reporter gene containing sequences targeted by different miRNA species in its 3′- untranslated region. We focus on the early time-course response (1 h past irradiation) to eliminate secondary mRNA expression waves. Results Experiments revealed that the irradiation-induced changes in the mRNA expression depend on the miRNAs which interact with mRNA. To identify the strongest interactions, we propose a mathematical model which predicts the mRNA fold expression changes, caused by perturbation of microRNA-mRNA interactions. Model was applied to experimental data including various cell lines, irradiation doses and observation times, both ours and literature-based. Comparison of modelled and experimental mRNA expression levels given miRNA level changes allows estimating how many and which miRNAs play a significant role in transcriptome response to stress conditions in different cell types. As an example, in the human melanoma cell line the comparison suggests that, globally, a major part of the irradiation-induced changes of mRNA expression can be explained by perturbed miRNA-mRNA interactions. A subset of about 30 out of a few hundred miRNAs expressed in these cells appears to account for the changes. These miRNAs play crucial roles in regulatory mechanisms observed after irradiation. In addition, these miRNAs have a higher average content of GC and a higher number of targeted transcripts, and many have been reported to play a role in the development of cancer. Conclusions Our proposed mathematical modeling approach may be used to identify miRNAs which participate in responses of cells to ionizing radiation, and other stress factors such as extremes of temperature, exposure to toxins, and drugs.

【 授权许可】

Unknown