Integrated analysis of mRNA and miRNA expression in response to interleukin-6 in hepatocytes

Lukowski, Samuel W.; Fish, Richard J.; Martin-Levilain, Juliette; Gonelle‐Gispert, Carmen; Bühler, Léo H.; Maechler, Pierre; Dermitzakis, Emmanouil T.; Neerman-Arbez, Marguerite

doi:10.1016/j.ygeno.2015.05.001

Cited by 15 publications

(18 citation statements)

References 48 publications

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“…This is in clear contrast to our previous understanding observed in other organisms [31, 32]. The discrepancy may be due to differences in organisms, tissue analyzed and experimental conditions.…”

Section: Introductioncontrasting

confidence: 99%

MicroRNAs regulate gene plasticity during cold shock in zebrafish larvae

et al. 2016

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BackgroundMicroRNAs (miRNAs) are critical regulators responding to acute environmental stresses in both plants and animals. By modulating gene expression, miRNAs either restore or reconstitute a new expression program to enhance cell tolerance to stresses. Cold shock is one of the stresses that can induce acute physiological responses and transcriptional changes in aquatic creatures. Previous genomic studies have revealed many cold-affected genes in fish larvae and adults, however, the role of miRNAs in acute cold response is still ambiguous. To elucidate the regulatory roles of miRNAs in the cold-inducible responses, we performed small RNA-seq and RNA-seq analyses and found potential cold regulatory miRNAs and genes. We further investigated their interactions and involvements in cold tolerance.ResultsSmall RNA-seq and RNA-seq identified 29 up-/26 down-regulated miRNAs and 908 up-/468 down-regulated genes, respectively, in responding to cold shock for 4 h at 18 °C. miRNA and transcriptomic analyses showed these miRNAs and mRNAs are involved in similar biological processes and pathways. Gene ontology enrichment analyses revealed the cold-induced genes were enriched in pathways, including melanogenesis, GnRH pathway, circadian rhythm, etc. We were particularly interested in the changes in circadian clock genes that affect daily metabolism. The enrichment of circadian clock genes was also observed in previous fish cold acclimation studies, but have not been characterized. To characterize the functional roles of circadian clock genes in cold tolerance, we individually overexpressed selected clock genes in zebrafish larvae and found one of the core clock genes per2 resulted in better recovery from cold shock. In addition, we validated the interaction of per2 with its associate miRNA, dre-mir-29b, which is also cold-inducible. It suggests the transcription of per2 can be modulated by miRNA upon cold shock.ConclusionsCollectively, our observations suggest that miRNAs are fine turners for regulating genomic plasticity against cold shock. We further showed that the fine tuning of core clock gene per2 via its associated miRNA, dre-mir-29b, can enhance the cold tolerance of zebrafish larvae.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3239-4) contains supplementary material, which is available to authorized users.

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Section: Introductioncontrasting

confidence: 99%

MicroRNAs regulate gene plasticity during cold shock in zebrafish larvae

et al. 2016

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“…Many of the acute-phase proteins are counter-regulated by hepatocyte growth factor (HGF), which plays a key role in liver growth and regeneration, but in primary human hepatocytes, HGF also suppressed α1-antichymotrypsin and haptoglobin, while increasing the synthesis of albumin, transferrin and fibronectin (5). The coordinated regulation of acute-phase protein genes is regulated in part by microRNAs that interact with the conserved 3’ UTR regions of those genes that are differentially expressed during the acute-phase response (6). …”

Section: The Acute Phasementioning

confidence: 99%

Hepatocytes as Immunological Agents

Crispe

2016

The Journal of Immunology

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Hepatocytes are targeted for infection by a number of major human pathogens, including Hepatitis B Virus, Hepatitis C Virus and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses including ischemia, physical trauma and sepsis. They express a variety of innate immune receptors and when challenged with Pathogen- or Damage-Associated Molecular Patterns, can deliver cell-autonomous innate immune responses that may result in host defense, or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias towards immune tolerance.

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“…Such processes can be studied through time course miRNA and mRNA data, since miRNAs play an important role in gene translation regulation in many organisms, through either mRNA translation inhibition or mRNA degradation29. This ability of miRNAs to fine tune gene expression and translation in a broad range of important biological processes is of broad interest in medicine303132. While correlation analysis is frequently used to analyse miRNA-mRNA time course data3334, it may have limited power in situations where delayed dynamic expression changes of miRNAs relative to mRNA have been observed3035.…”

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DynOmics to identify delays and co-expression patterns across time course experiments

Straube

Huang

Cao

2017

Sci Rep

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Dynamic changes in biological systems can be captured by measuring molecular expression from different levels (e.g., genes and proteins) across time. Integration of such data aims to identify molecules that show similar expression changes over time; such molecules may be co-regulated and thus involved in similar biological processes. Combining data sources presents a systematic approach to study molecular behaviour. It can compensate for missing data in one source, and can reduce false positives when multiple sources highlight the same pathways. However, integrative approaches must accommodate the challenges inherent in ‘omics’ data, including high-dimensionality, noise, and timing differences in expression. As current methods for identification of co-expression cannot cope with this level of complexity, we developed a novel algorithm called DynOmics. DynOmics is based on the fast Fourier transform, from which the difference in expression initiation between trajectories can be estimated. This delay can then be used to realign the trajectories and identify those which show a high degree of correlation. Through extensive simulations, we demonstrate that DynOmics is efficient and accurate compared to existing approaches. We consider two case studies highlighting its application, identifying regulatory relationships across ‘omics’ data within an organism and for comparative gene expression analysis across organisms.

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Integrated analysis of mRNA and miRNA expression in response to interleukin-6 in hepatocytes

Cited by 15 publications

References 48 publications

MicroRNAs regulate gene plasticity during cold shock in zebrafish larvae

MicroRNAs regulate gene plasticity during cold shock in zebrafish larvae

Hepatocytes as Immunological Agents

DynOmics to identify delays and co-expression patterns across time course experiments

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