Abstract
The aim of this work was to establish the microRNA profile of SNK6 and SNT16, two Epstein–Barr virus (EBV)‐infected cell lines derived from nasal NK/T‐cell lymphoma (NKTL). The oncogenic EBV is strongly associated with the pathogenesis of nasal and extranodal NK/T‐cell lymphoma and expresses 44 mature microRNAs and two noncoding EBV‐encoded RNAs (EBERs). miRNAs are 19‐25nt noncoding RNAs that affect host and viral gene expression post‐transcriptionally. Deregulated miRNA patterns are frequently linked to a variety of human cancers including lymphomas. miRNA profiling of the two NK/T cell lines vs. primary cells revealed 10 and 4 up‐regulated and 10 and 12 down‐regulated miRNAs in SNK6 and SNT16 cells respectively. The results were validated by qRT‐PCR for selected miRNAs. Target gene analyses confirmed cullin 5 (CUL5) and sphingosin‐1‐phosphate receptor 1 (S1PR1) as targets for the down‐regulated hsa‐miR‐148a and viral ebv‐miR‐BART16 respectively. As recently demonstrated for the regulation of IL1‐alpha by miR‐142‐3p, coexpression of the EBERs selectively exerted corepression of S1PR1 by BART16 but not of CUL5 by miR‐148a, indicating selective corepression by the EBERs.
Highlights
Julia Alles1, Jennifer Menegatti1, Natalie Motsch1,*, Martin Hart1, Norbert Eichner2, Richard Reinhardt3, Gunter Meister2 and Friedrich A
The aim of this work was to establish the microRNA profile of SNK6 and SNT16, two Epstein–Barr virus (EBV)-infected cell lines derived from nasal NK/T-cell lymphoma (NKTL)
For the sphingosin-1-phosphate receptor 1 (S1PR1), we find that co-expression of the Epstein–Barr virus-encoded RNA (EBER) further represses down-regulation of both a 30UTR reporter and the protein by ebv-miR-BART16, while the EBERs show no additional effect on the repression of a 30UTR cullin-5 (CUL5) reporter by miR-148a
Summary
The aim of this work was to establish the microRNA profile of SNK6 and SNT16, two Epstein–Barr virus (EBV)-infected cell lines derived from nasal NK/T-cell lymphoma (NKTL). EBV is strongly associated with a type of non-Hodgkin’s Lymphoma: the very rare NK/ T-cell lymphoma (NKTL). Those tumours derive from NK- and/or T cells [4] and occur predominantly in Asia and Central-/South America. MiRNA profiling of two EBV-infected NKTL cell lines the upper aerodigestive tract is often affected by a high grade of necrosis [5] as a consequence of perforin [6] or granzyme B expression [7]. Cases of extranodal NKTL of the gastro-intestinal tract, skin, testis, lung, eye or soft tissue have been reported [8,9,10,11,12])
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