Identification of miR-221 and -222 as important regulators in genotype IV swine hepatitis E virus ORF3-expressing HEK 293 cells

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• 作者：Ying Cheng (1)
  Li Du (1)
  Qiaoyun Shi (1)
  Hanwei Jiao (1)
  Xiaoru Zhang (1)
  Yongchang Hao (1)
  Hui Rong (1)
  Jianing Zhang (1)
  Xiaoxiao Jia (1)
  Shiyu Guo (1)
  Wenhua Kuang (1)
  Hui Zhang (2)
  Chuangfu Chen (2)
  Fengyang Wang (1)
  
• 关键词：SHEV ; Genotype IV ; ORF3 ; miR ; 221 and ; 222 ; p27kip1
• 刊名：Virus Genes
• 出版年：2013
• 出版时间：August 2013
• 年：2013
• 卷：47
• 期：1
• 页码：49-55
• 全文大小：489KB
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• 作者单位：Ying Cheng (1)
  Li Du (1)
  Qiaoyun Shi (1)
  Hanwei Jiao (1)
  Xiaoru Zhang (1)
  Yongchang Hao (1)
  Hui Rong (1)
  Jianing Zhang (1)
  Xiaoxiao Jia (1)
  Shiyu Guo (1)
  Wenhua Kuang (1)
  Hui Zhang (2)
  Chuangfu Chen (2)
  Fengyang Wang (1)
  
  1. College of Agriculture, Hainan University, Hainan Key Lab of Tropical Animal Reproduction & Breeding and Epidemic Disease Research, Animal Genetic Engineering Key Lab of Haikou, Haidian Island, Haikou, 570228, People鈥檚 Republic of China
  2. College of Animal Science and Technology, Shihezi University, North 4th Road, Shihezi, 832003, People鈥檚 Republic of China
  

文摘

Hepatitis E virus (HEV) has emerged as an important cause of epidemic and sporadic acute viral hepatitis worldwide, which is a major public health challenge. A better understanding of the interaction between the virus and the host cell would be very helpful for its therapy. Swine HEV (SHEV) open reading frame 3 (ORF3) is a regulatory protein that alters the activity of selected transcription factors and cytoplasmic signaling pathways. MicroRNAs (miRNAs) are potent post-transcriptional regulators of protein-coding genes and represent an interesting lead to study SHEV infection and to identify new therapeutic targets. To explore how SHEV ORF3 affects miRNAs in host cells, we used miRNA array analysis to compare the expression patterns of miRNAs in stable cell lines that expressed or did not express SHEV ORF3. We found a significant down-regulation of miR-221 and -222 in ORF3 expressing human embryonic kidney 293 cell line. Among the 116 candidate targets genes of miR-221 and -222 that we detected in silico, we demonstrated that the expression of the cyclin-dependent kinase inhibitor 1B, also named p27kip1, was directly regulated by these miRNAs. We hypothesize that SHEV ORF3-induced miR-221/222 downregulation enhances p27kip1 expression in HEK293 cells. This provides new avenues for future exploration of the precise roles of miRNAs in SHEV infection.