title: Proteomic screening of human targets of viral microRNAs reveals functions associated with immune evasion and angiogenesis.
abstract: Kaposi's sarcoma (KS) is caused by infection with Kaposi's sarcoma-associated herpesvirus (KSHV). The virus expresses unique microRNAs (miRNAs), but the targets and functions of these miRNAs are not completely understood. In order to identify human targets of viral miRNAs, we measured protein expression changes caused by multiple KSHV miRNAs using pulsed stable labeling with amino acids in cell culture (pSILAC) in primary endothelial cells. This led to the identification of multiple human genes that are repressed at the protein level, but not at the miRNA level. Further analysis also identified that KSHV miRNAs can modulate activity or expression of upstream regulatory factors, resulting in suppressed activation of a protein involved in leukocyte recruitment (ICAM1) following lysophosphatidic acid treatment, as well as up-regulation of a pro-angiogenic protein (HIF1α), and up-regulation of a protein involved in stimulating angiogenesis (HMOX1). This study aids in our understanding of miRNA mechanisms of repression and miRNA contributions to viral pathogenesis.
authors.affiliation: HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Amelia M
authors.initials: AM
authors.lastname: Gallaher
authors.forename: Sudipto
authors.initials: S
authors.lastname: Das
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xiao
authors.forename: Thorkell
authors.initials: T
authors.lastname: Andresson
authors.forename: Philippe
authors.initials: P
authors.lastname: Kieffer-Kwon
authors.forename: Christine
authors.initials: C
authors.lastname: Happel
authors.forename: Joseph
authors.initials: J
authors.lastname: Ziegelbauer
mesh_terms: D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019139:Tumor Escape
chemical_list: D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D012367:RNA, Viral
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