MicroRNA expression profile of human umbilical vein endothelial cells in response to coxsackievirus A10 infection reveals a potential role of miR-143-3p in maintaining the integrity of the blood–brain barrier

Frontiers in Cellular and Infection Microbiology

Cellular and Infection Microbiology

Fengxian Cui¹  Chen Liu²  Yunhui Zhang²  Ruiqi Wang²  Shengxiong Zhang²  Shenglan Wang²  Yajie Hu³  Jie Song⁴ 

[1]Department of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province, Kunming, China

[2]Department of Thoracic Surgery, The First People’s Hospital of Yunnan Province, Kunming, China

[3]Department of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province, Kunming, China

[4]The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China

[5]Department of Pulmonary and Critical Care Medicine, The First People’s Hospital of Yunnan Province, Kunming, China

[6]The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China

[7]Yunnan Provincial Key Laboratory of Clinical Virology, The First People’s Hospital of Yunnan Province, Kunming, China

[8]Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming, China

关键词: hand;    foot;    and mouth disease (HFMD);    coxsackievirus A10 (CV-A10);    microRNAs (miRNAs);    high-throughput sequencing;    blood–brain barrier (BBB);   

DOI  :  10.3389/fcimb.2023.1217984

 received in 2023-05-06, accepted in 2023-07-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

Coxsackievirus A10 (CV-A10) has been one of the main etiologies of hand, foot, and mouth disease (HFMD) epidemics in recent years and can cause mild to severe illness and even death. Most of these severe and fatal cases were closely associated with neurological impairments, but the potential mechanism of neuropathological injury triggered by CV-A10 infection has not been elucidated. MicroRNAs (miRNAs), implicated in the regulation of gene expression in a post-transcriptional manner, play a vital role in the pathogenesis of various central nervous system (CNS) diseases; therefore, they serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. To gain insights into the CV-A10-induced regulation of host miRNA-processing machinery, we employed high-throughput sequencing to identify differentially expressed miRNAs in CV-A10-infected human umbilical vein endothelial cells (HUVECs) and further analyzed the potential functions of these miRNAs during CV-A10 infection. The results showed that CV-A10 infection could induce 189 and 302 significantly differentially expressed miRNAs in HUVECs at 24 and 72 hpi, respectively, compared with the uninfected control. Moreover, the expression of four selected miRNAs and their relevant mRNAs was determined to verify the sequencing data by quantitative reverse transcription–polymerase chain reaction (RT–qPCR) methods. After that, gene target prediction and functional annotation revealed that the targets of these dysregulated miRNAs were mostly enriched in cell proliferation, signal transduction, cAMP signalling pathway, cellular response to interleukin-6, ventral spinal cord interneuron differentiation, negative regulation of glial cell differentiation, neuron migration, positive regulation of neuron projection development, etc., which were primarily involved in the processes of basic physiology, host immunity, and neurological impairments and further reflected vital regulatory roles of miRNA in viral pathogenicity. Finally, the construction of a miRNA-regulated network also suggested that the complex regulatory mechanisms mediated by miRNAs might be involved in viral pathogenesis and virus–host interactions during CV-A10 infection. Furthermore, among these dysregulated miRNAs, miR-143-3p was demonstrated to be involved in the maintenance of blood–brain barrier (BBB) integrity.

【 授权许可】

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Copyright © 2023 Hu, Cui, Wang, Liu, Zhang, Wang, Song and Zhang