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Human cytomegalovirus-encoded miR-UL112 contributes to HCMV-mediated vascular diseases by inducing vascular endothelial cell dysfunction

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Abstract

Human cytomegalovirus (HCMV) infection has been linked to the pathogenesis of vasculopathy by inducing dysfunction of vascular cells such as endothelial cells. Hcmv-miR-UL112 is the most well-characterized HCMV-encoded microRNA occurring in the plasma of patients with cardiovascular diseases such as hypertension, while the specific underlying pathophysiological mechanisms are yet to be defined. The current study investigated the effect of hcmv-miR-UL112 on the growth and proliferation of human umbilical vascular endothelial cells (HUVECs); it might also be associated with signaling pathways. An adenovirus vector was designed and synthesized to stably express hcmv-miR-UL112 in HUVECs. Cell Counting Kit-8 results showed that ectopically expressed hcmv-miR-UL112 can significantly increase the proliferation of HUVECs (p < 0.05). Flow cytometry revealed that the S-phase fraction in the cell cycle analysis was raised significantly after overexpression of hcmv-miR-UL112 (p < 0.05). Gene expression profile analysis, using the microarray technology, revealed 303 up-regulated and 62 down-regulated genes in HUVECs by comparing the AD-hcmv-miR-UL112-infected and control groups (p < 0.05 and > 2 fold change). Kyoto Encyclopedia of Genes and Genomes and Reactome Pathway, chosen as the functional annotation categories, were affected by hcmv-miR-UL112 adenovirus vector. The significantly altered pathways mainly include the mitogen-activated protein kinase signaling pathway, cell adhesion molecules, chemokine signaling pathway, cytokine–cytokine receptor interaction, circadian rhythm-mammal, mineral absorption, protein processing in the endoplasmic reticulum, proximal tubule bicarbonate reclamation, vasopressin-regulated water reabsorption, and arachidonic acid metabolism. In conclusion, hcmv-miR-UL112 could serve as a potential biomarker, and the miRNA-mediated regulation of signaling pathways might play significant roles in the physiological effects of hcmv-associated diseases.

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Acknowledgements

This work was supported by grants from the Zhejiang Provincial Natural Science Foundation of China [Nos. LY13H020001 and LQ13H100001] and the Science and Technology Bureau of Zhoushan [No. 2012C13024].

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Author notes

  1. Kai Shen and Liyun Xu contributed equally to this article.

Authors and Affiliations

  1. Department of cardiovascular internal medicine, Zhoushan Hospital, Zhoushan, 316021, Zhejiang, China

    Kai Shen

  2. Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhoushan, 316021, Zhejiang, China

    Liyun Xu, Dongdong Chen & Yanyan Huang

  3. Department of Neurology, Zhoushan Hospital, Zhoushan, 316021, Zhejiang, China

    Weiguo Tang

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  1. Kai Shen
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Contributions

KS and LX contributed equally in performing cytology experiments and data analysis, DC undertook flow cytometry, WT was responsible for microarray data analysis, and YH is the corresponding author of this article.

Corresponding author

Correspondence to Yanyan Huang.

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The authors declare that they have no competing interests.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Edited by Hartmut Hengel.

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Table S1

The complete list of significant up-regulation genes in AD-hcmv-miR-UL112 transfected HUVECs. The gene expression profiling of AD-hcmv-miR-UL112 transfected HUVECs was compared with that of negative control groups. Supplementary material 1 (DOC 557 kb)

Table S2

The complete list of significant down-regulation genes in AD-hcmv-miR-UL112 transfected HUVECs. The gene expression profiling of AD-hcmv-miR-UL112 transfected HUVECs was compared with that of negative control groups. Supplementary material 2 (DOC 121 kb)

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Shen, K., Xu, L., Chen, D. et al. Human cytomegalovirus-encoded miR-UL112 contributes to HCMV-mediated vascular diseases by inducing vascular endothelial cell dysfunction. Virus Genes 54, 172–181 (2018). https://doi.org/10.1007/s11262-018-1532-9

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  • DOI: https://doi.org/10.1007/s11262-018-1532-9

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