title: MicroRNA profiling of Epstein-Barr virus-associated NK/T-cell lymphomas by deep sequencing.
abstract: The Epstein-Barr virus (EBV) is an oncogenic human Herpes virus involved in the pathogenesis of nasal NK/T-cell lymphoma. EBV encodes microRNAs (miRNAs) and induces changes in the host cellular miRNA profile. MiRNAs are short non-coding RNAs of about 19-25 nt length that regulate gene expression by post-transcriptional mechanisms and are frequently deregulated in human malignancies including cancer. The microRNA profiles of EBV-positive NK/T-cell lymphoma, non-infected T-cell lymphoma and normal thymus were established by deep sequencing of small RNA libraries. The comparison of the EBV-positive NK/T-cell vs. EBV-negative T-cell lymphoma revealed 15 up- und 16 down-regulated miRNAs. In contrast, the majority of miRNAs was repressed in the lymphomas compared to normal tissue. We also identified 10 novel miRNAs from known precursors and two so far unknown miRNAs. The sequencing results were confirmed for selected miRNAs by quantitative Real-Time PCR (qRT-PCR). We show that the proinflammatory cytokine interleukin 1 alpha (IL1A) is a target for miR-142-3p and the oncogenic BCL6 for miR-205. MiR-142-3p is down-regulated in the EBV-positive vs. EBV-negative lymphomas. MiR-205 was undetectable in EBV-negative lymphoma and strongly down-regulated in EBV-positive NK/T-cell lymphoma as compared to thymus. The targets were confirmed by reporter assays and by down-regulation of the proteins by ectopic expression of the cognate miRNAs. Taken together, our findings demonstrate the relevance of deregulated miRNAs for the post-transcriptional gene regulation in nasal NK/T-cell lymphomas.
authors.affiliation: Institute of Microbiology and Hygiene, Department of Virology, University Hospital of Saarland University, Homburg/Saar, Germany.
authors.forename: Natalie
authors.initials: N
authors.lastname: Motsch
authors.forename: Julia
authors.initials: J
authors.lastname: Alles
authors.forename: Jochen
authors.initials: J
authors.lastname: Imig
authors.forename: Jiayun
authors.initials: J
authors.lastname: Zhu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Barth
authors.forename: Tanja
authors.initials: T
authors.lastname: Reineke
authors.forename: Marianne
authors.initials: M
authors.lastname: Tinguely
authors.forename: Sergio
authors.initials: S
authors.lastname: Cogliatti
authors.forename: Anne
authors.initials: A
authors.lastname: Dueck
authors.forename: Gunter
authors.initials: G
authors.lastname: Meister
authors.forename: Christoph
authors.initials: C
authors.lastname: Renner
authors.forename: Friedrich A
authors.initials: FA
authors.lastname: Grässer
mesh_terms: D045744:Cell Line, Tumor; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human; D006801:Humans; D053582:Interleukin-1alpha / Q000096:biosynthesis / Q000235:genetics; D054391:Lymphoma, Extranodal NK-T-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D017423:Sequence Analysis, RNA
chemical_list: D053582:Interleukin-1alpha; D035683:MicroRNAs; D012334:RNA, Neoplasm; C508584:IL1A protein, human; C555159:MIRN142 microRNA, human; C534425:MIR205, human