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

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dc.citation.articleNumber114en_US
dc.citation.journalTitleBMC Genomicsen_US
dc.citation.volumeNumber20en_US
dc.contributor.authorMura, Marzenaen_US
dc.contributor.authorJaksik, Romanen_US
dc.contributor.authorLalik, Annaen_US
dc.contributor.authorBiernacki, Krzysztofen_US
dc.contributor.authorKimmel, Mareken_US
dc.contributor.authorRzeszowska-Wolny, Joannaen_US
dc.contributor.authorFujarewicz, Krzysztofen_US
dc.date.accessioned2019-12-12T17:25:39Zen_US
dc.date.available2019-12-12T17:25:39Zen_US
dc.date.issued2019en_US
dc.description.abstractBackground: 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.en_US
dc.identifier.citationMura, Marzena, Jaksik, Roman, Lalik, Anna, et al.. "A mathematical model as a tool to identify microRNAs with highest impact on transcriptome changes." <i>BMC Genomics,</i> 20, (2019) BioMed Central: https://doi.org/10.1186/s12864-019-5464-0.en_US
dc.identifier.digitals12864-019-5464-0en_US
dc.identifier.doihttps://doi.org/10.1186/s12864-019-5464-0en_US
dc.identifier.urihttps://hdl.handle.net/1911/107890en_US
dc.language.isoengen_US
dc.publisherBioMed Centralen_US
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/),en_US
dc.titleA mathematical model as a tool to identify microRNAs with highest impact on transcriptome changesen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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