title: Marek's disease virus-encoded analog of microRNA-155 activates the oncogene c-Myc by targeting LTBP1 and suppressing the TGF-β signaling pathway.
abstract: Marek's disease virus (MDV) is a representative alpha herpes virus able to induce rapid-onset T-cell lymphoma in its natural host and regarded as an ideal model for the study of virus-induced tumorigenesis. Recent studies have shown that the mdv1-miR-M4-5p, a viral analog of cellular miR-155, is critical for MDV׳s oncogenicity. However, the precise mechanism whereby it was involved in MD lymphomagenesis remained unknown. We have presently identified the host mRNA targets of mdv1-miR-M4-5 and identified the latent TGF-β binding protein 1 (LTBP1) as a critical target for it. We found that during MDV infection, down-regulation of LTBP1 expression by mdv1-miR-M4-5p led to a significant decrease of the secretion and activation of TGF-β1, with suppression of TGF-β signaling and a significant activation of expression of c-Myc, a well-known oncogene which is critical for virus-induced tumorigenesis. Our findings reveal a novel and important mechanism of how mdv1-miR-M4-5p potentially contributes to MDV-induced tumorigenesis.
authors.affiliation: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, People׳s Republic of China; Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, People׳s Republic of China; College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, People׳s Republic of China.
authors.forename: Jia-Qi
authors.initials: JQ
authors.lastname: Chi
authors.affiliation: Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, People׳s Republic of China.
authors.forename: Man
authors.initials: M
authors.lastname: Teng
authors.affiliation: College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, People׳s Republic of China; Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, People׳s Republic of China.
authors.forename: Zu-Hua
authors.initials: ZH
authors.lastname: Yu
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People׳s Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, People׳s Republic of China; College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, People׳s Republic of China.
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Su
authors.affiliation: Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, People׳s Republic of China; College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, People׳s Republic of China.
authors.forename: Pu
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, People׳s Republic of China.
authors.forename: Guang-Xu
authors.initials: GX
authors.lastname: Xing
authors.affiliation: College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, People׳s Republic of China.
authors.forename: Hong-De
authors.initials: HD
authors.lastname: Liang
authors.affiliation: Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, People׳s Republic of China.
authors.forename: Rui-Guang
authors.initials: RG
authors.lastname: Deng
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Science, Sun Yat-Sen (Zhongshan) University, Guangzhou 510275, People׳s Republic of China.
authors.forename: Liang-Hu
authors.initials: LH
authors.lastname: Qu
authors.affiliation: College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, People׳s Republic of China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, People׳s Republic of China. Electronic address: zhanggaiping2003@163.com.
authors.forename: Gai-Ping
authors.initials: GP
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou 450002, People׳s Republic of China. Electronic address: luojun593@aliyun.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Luo
mesh_terms: D000818:Animals; D001483:Base Sequence; D002645:Chickens; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D053779:Latent TGF-beta Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008380:Marek Disease / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016274:Oncogene Protein p55(v-myc) / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D053779:Latent TGF-beta Binding Proteins; D035683:MicroRNAs; D016274:Oncogene Protein p55(v-myc); D012367:RNA, Viral; D016212:Transforming Growth Factor beta
keywords: LTBP1; MDV; MicroRNA; Oncogenesis; TGF-β signaling; mdv1-miR-M4-5p; miR-155