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miR-539 as a key negative regulator of the MEK pathway in myocardial infarction

miR-539 als entscheidender negativer Regulator des MEK-Signalwegs beim Myokardinfarkt

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Abstract

Background

Myocardial infarction is one of the most common causes of death, and the number of individuals at risk is increasing. A rapid and accurate differential diagnosis of myocardial infarction is crucial for timely interventions and for improvement of the prognosis. However, it is difficult to achieve using current methods. To better manage this condition, improved tools for risk prediction, including more accurate biomarkers, are needed.

Methods

We studied the expression of microRNA-539 (miR-539) and of MEK protein using a rat model of myocardial infarction.

Results

The results of our experiments demonstrated an increase in the expression of miR-539 and a decrease in the expression of MEK. Furthermore, we observed that miR-539 inhibited the expression of MEK through targeting of the 3’UTR of MEK; this led not only to suppressed proliferation but also to apoptosis and autophagy of H9C2 cells.

Conclusion

Overexpression of miR-539 plays a role in the degree of myocardial infarction. On the basis of our results, we conclude that miR-539 may be a potential therapeutic target for myocardial infarction.

Zusammenfassung

Hintergrund

Der Myokardinfarkt ist eine der häufigsten Todesursachen, und die Anzahl dadurch gefährdeter Patienten steigt. Eine schnelle und genaue Differenzialdiagnostik des Myokardinfarkts ist für rechtzeitige Interventionen und somit für eine bessere Prognose entscheidend. Jedoch ist dies mit den derzeit eingesetzten Verfahren schwer zu erreichen. Um einen Myokardinfarkt besser zu behandeln, sind verbesserte Instrumente der Risikovorhersage einschließlich genauerer Biomarker notwendig.

Methoden

Untersucht wurde die Expression von microRNA-539 (miR-539) und des MEK-Proteins anhand eines Rattenmodells für Myokardinfarkt.

Ergebnisse

Die Ergebnisse der vorliegenden Experimente zeigten eine Zunahme der Expression von miR-539 und eine Abnahme der Expression von MEK. Darüber hinaus stellten die Autoren fest, dass miR-539 die Expression von MEK durch Ansatz an der 3’UTR („3’-untranslated region“) von MEK hemmte, was nicht nur zu einer Unterdrückung der Proliferation, sondern auch zur Apoptose und Autophagie von H9C2-Zellen führte.

Schlussfolgerung

Die Überexpression von miR-539 ist für das Ausmaß des Myokardinfarkts von Bedeutung. Nach den hier vorliegenden Ergebnissen kommen die Autoren zu dem Schluss, dass miR-539 ein potenzielles therapeutisches Ziel beim Myokardinfarkt darstellen könnte.

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Acknowledgements

This research was sponsored by the Science and Technology Project of Liaoning Province (2013225089).

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Authors and Affiliations

  1. Department of Cardiovascular Surgery, The General Hospital of Shenyang Military Region, No. 83Wenhua Road, 110016, Shenhe District, Shenyang, Liaoning, China

    J. Hui, W. Huishan PhD, L. Tao, Y. Zhonglu, Z. Renteng & H. Hongguang

Authors
  1. J. Hui
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  2. W. Huishan PhD
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  3. L. Tao
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  4. Y. Zhonglu
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  5. Z. Renteng
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  6. H. Hongguang
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Corresponding author

Correspondence to W. Huishan PhD.

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Conflict of interest

J. Hui, W. Huishan, L. Tao, Y. Zhonglu, Z. Renteng, and H. Hongguang declare that they have no competing interests.

This animal study received China medical university animal care and use committee approval. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Additional information

Authors’ contributions Hui Jiang conceived of the study, carried out the molecular studies, Huishan Wang carried out the molecular studies and helped to draft the manuscript. Tao Liu participated in the design of the study and performed the statistical analysis. Zhonglu Yang participated in its design and coordination and helped to draft the manuscript. Renteng Zhang and Hongguang Han conceived of the study.

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Hui, J., Huishan, W., Tao, L. et al. miR-539 as a key negative regulator of the MEK pathway in myocardial infarction. Herz 42, 781–789 (2017). https://doi.org/10.1007/s00059-016-4517-2

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  • DOI: https://doi.org/10.1007/s00059-016-4517-2

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