title: Identification of miR-221 and -222 as important regulators in genotype IV swine hepatitis E virus ORF3-expressing HEK 293 cells.
abstract: 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 p27(kip1), was directly regulated by these miRNAs. We hypothesize that SHEV ORF3-induced miR-221/222 downregulation enhances p27(kip1) expression in HEK293 cells. This provides new avenues for future exploration of the precise roles of miRNAs in SHEV infection.
authors.affiliation: College of Agriculture, Hainan University, Hainan Key Lab of Tropical Animal Reproduction & Breeding and Epidemic Disease Research, Haidian Island, Haikou 570228, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Li
authors.initials: L
authors.lastname: Du
authors.forename: Qiaoyun
authors.initials: Q
authors.lastname: Shi
authors.forename: Hanwei
authors.initials: H
authors.lastname: Jiao
authors.forename: Xiaoru
authors.initials: X
authors.lastname: Zhang
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Hao
authors.forename: Hui
authors.initials: H
authors.lastname: Rong
authors.forename: Jianing
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Jia
authors.forename: Shiyu
authors.initials: S
authors.lastname: Guo
authors.forename: Wenhua
authors.initials: W
authors.lastname: Kuang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Chuangfu
authors.initials: C
authors.lastname: Chen
authors.forename: Fengyang
authors.initials: F
authors.lastname: Wang
mesh_terms: D000818:Animals; D001483:Base Sequence; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression; D057809:HEK293 Cells; D016751:Hepatitis E / Q000235:genetics / Q000378:metabolism / Q000662:veterinary* / Q000821:virology*; D016752:Hepatitis E virus / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D013552:Swine; D013553:Swine Diseases / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D050760:Cyclin-Dependent Kinase Inhibitor p27; D035683:MicroRNAs; D014764:Viral Proteins; C525709:MIR221, human; C525710:MIR222, human; C400973:ORF3 protein, Hepatitis E virus