Enterovirus 71 Suppresses miR-17-92 Cluster Through Up-Regulating Methylation of the miRNA Promoter.

Authors:
Yuxuan Fu
Yuxuan Fu
Nanjing Medical University
Nanjing Shi | China
Li Zhang
Li Zhang
Dongfang Hospital Affiliated to Beijing University of Chinese Medicine
China
Rui Zhang
Rui Zhang
Cancer Hospital of China Medical University
Houston | United States
Shijie Xu
Shijie Xu
Institute of Basic Research in Clinical Medicine
China
Huanru Wang
Huanru Wang
Center for Public Health Research
Yu Jin
Yu Jin
Shengjing Hospital of China Medical University
China
Zhiwei Wu
Zhiwei Wu
School of Medicine
China

Front Microbiol 2019 28;10:625. Epub 2019 Mar 28.

School of Life Sciences, Ningxia University, Yinchuan, China.

Enterovirus 71 (EV71), the etiological agent of hand-foot-and-mouth disease, has become an increasing public health challenge worldwide. Accumulating evidence suggests that mammalian microRNAs (miRNAs), a class of non-coding RNAs of 18 to 24 nucleotides (nt) with important regulatory roles in cellular processes, participate in host antiviral defense and studies have suggested roles of miRNAs in EV71 replication and pathogenesis. In the current study, we reported that the expression of hsa-miR-17∼92 cluster was significantly downregulated during EV71 infection. Overexpression of hsa-miR-17∼92 inhibited, while inhibition of endogenous hsa-miR-17∼92 facilitated EV71 replication. We identified two sequences located at nt 3024 to 3038 and nt 2838 to 2862 of the EV71 (strain FY0805) genome as potential targets for hsa-miR-17-5p and miR-19a/b, respectively, which were validated by luciferase reporter assays and Western blot. Meanwhile, we identified DNA methylation as a novel mechanism of hsa-miR-17∼92 regulatory roles. The methylation of the miR-17-92 promoter was significantly increased (50%) upon EV71 infection, which appeared to be caused by the increased expression of DNMT3B but not DNMT1 and DNMT3A. Furthermore, we demonstrated that the members of miR-17-92 cluster were decreased in the sera of EV71 infected patients, suggesting the clinical implication and the potential therapeutic application of miR-17-92.

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https://www.frontiersin.org/article/10.3389/fmicb.2019.00625
Publisher Site
http://dx.doi.org/10.3389/fmicb.2019.00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447709PMC
March 2019
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References

(Supplied by CrossRef)
DNA methylation regulates MicroRNA expression.
Han et al.
Cancer Biol. Ther. 2007

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