MiR-608 Exerts Anti-inflammatory Effects by Targeting ELANE in Monocytes
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miR-608 has been indicated to play an important role in the pathogenesis of various inflammation-related diseases, including sepsis and several types of cancers. However, there is little information about the underlying mechanism, especially in inflammatory cells. In this study, an hsa-miR-608-inhibition cell model was constructed in U937 cells using a lentivirus, and gene expression profiles were determined by a cDNA microarray. Altogether, 682 genes showed a difference greater than 1.2-fold, including 184 genes downregulated and 498 genes upregulated. Among these genes, one potential miR-608-target gene, ELANE, was further investigated. A positive relationship between the expression of miR-608 and that of ELANE was found both in vivo and in vitro. In addition, decreased expression of miR-608 resulted in overexpression of ELANE at both the mRNA and protein levels. Cotransfection of HEK293T cells with a miR-608 mimic inhibited reporter activity, and mutation of the miRNA seed sequences abolished the repression of reporter activity. These results suggest that miR-608 is an important posttranscriptional regulator of ELANE expression in human monocytes and may play an important role in the process of inflammation. miR-608 and neutrophil elastase may be novel targets for the diagnosis or treatment of sepsis.
KeywordsSepsis miR-608 ELANE microRNAs microarray
Author Contribution Statement
W. G. and J.-X. J. designed the experiments. W. G., D.-L. W., X. W., H.-Y. W., and J.D. performed the experiments. W. G. A.-Q. Z. and L. Z. analyzed the data. W.G. wrote the manuscript. J.-X. J. contributed to editing the manuscript. All the authors have reviewed and approved the final version of this manuscript.
This work is supported by the National Natural Science Foundation of China (81272076, 81471861), the Promotion of Scientific Research Ability of Young Teachers and Excellent Students in Bioengineering College, Science and Technology Innovation Project for Academicians of Chongqing (cstc2019jcyj-msxmX0266), Cross-Team Cultivation and Scientific and Technological Infrastructure Construction (2019CDXYSG0004), and the Key Research Project of the “Twelfth Five-Year Plan” of the PLA (CWS12J092, AWS14C001).
Compliance with Ethical Standards
The study and methods were approved by the Ethical and Protocol Review Committee of the Third Military Medical University (No. 009, 2012) according to the standards of the Declaration of Helsinki for medical research involving human subjects. Informed consent was obtained from all subjects.
Conflict of Interest
The authors declare that they have no conflict of interest.
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