title: Knock-Down of Endogenous Bornavirus-Like Nucleoprotein 1 Inhibits Cell Growth and Induces Apoptosis in Human Oligodendroglia Cells.
abstract: Endogenous bornavirus-like nucleoprotein elements (EBLNs) have been discovered in the genomes of various animals including humans, whose functions have been seldom studied. To explore the biological functions of human EBLNs, we constructed a lentiviral vector expressing a short-hairpin RNA against human EBLN1, which successfully inhibited EBLN1 expression by above 80% in infected human oligodendroglia cells (OL cells). We found that EBLN1 silencing suppressed cell proliferation, induced G2/M phase arrest, and promoted apoptosis in OL cells. Gene expression profiling demonstrated that 1067 genes were up-regulated, and 2004 were down-regulated after EBLN1 silencing. The top 10 most upregulated genes were PI3, RND3, BLZF1, SOD2, EPGN, SBSN, INSIG1, OSMR, CREB3L2, and MSMO1, and the top 10 most-downregulated genes were KRTAP2-4, FLRT2, DIDO1, FAT4, ESCO2, ZNF804A, SUV420H1, ZC3H4, YAE1D1, and NCOA5. Pathway analysis revealed that these differentially expressed genes were mainly involved in pathways related to the cell cycle, the mitogen-activated protein kinase pathway, p53 signaling, and apoptosis. The gene expression profiles were validated by using quantitative reverse transcription polymerase chain reaction (RT-PCR) for detecting these 20 most-changed genes. Three genes closely related to glioma, RND3, OSMR, and CREB3L2, were significantly upregulated and might be the key factors in EBLN1 regulating the proliferation and apoptosis of OL cells. This study provides evidence that EBLN1 plays a key role in regulating cell life and death, thereby opening several avenues of investigation regarding EBLN1 in the future.
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China. hepeng000@sina.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. hepeng000@sina.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. hepeng000@sina.com.
authors.forename: Peng
authors.initials: P
authors.lastname: He
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. tilamisu789456123@126.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. tilamisu789456123@126.com.|Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. tilamisu789456123@126.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. zhudan25@126.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. zhudan25@126.com.|Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. zhudan25@126.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. ASDFG43215@126.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. ASDFG43215@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. zhlbright@gmail.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. zhlbright@gmail.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. g1240725344@163.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. g1240725344@163.com.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. 18983145528@163.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. 18983145528@163.com.
authors.forename: Siwen
authors.initials: S
authors.lastname: Liu
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. duduzjj@163.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. duduzjj@163.com.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. xxy2922@163.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. xxy2922@163.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China. xiepeng@cqmu.edu.cn.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. xiepeng@cqmu.edu.cn.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. xiepeng@cqmu.edu.cn.|Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. xiepeng@cqmu.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D015536:Down-Regulation; D059565:G2 Phase Cell Cycle Checkpoints; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D009698:Nucleoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D053681:Oncostatin M Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D050976:Basic-Leucine Zipper Transcription Factors; C518609:CREB3L2 protein, human; C000612894:EBLN1 protein, human; D009698:Nucleoproteins; C508348:OSMR protein, human; D053681:Oncostatin M Receptor beta Subunit; D034741:RNA, Small Interfering; D020928:Mitogen-Activated Protein Kinases; C508705:RND3 protein, human; D020741:rho GTP-Binding Proteins
keywords: RNA interference; apoptosis; cDNA array; cell proliferation; endogenous bornavirus-like nucleoprotein 1