ArrayExpress Uploaderarrayexpress_sid502504MicroRNAs are small, non-coding RNAs that post-transcriptionally regulate gene expression by binding to 3’UTRs of target mRNAs. Kaposi’s...17881434E-GEOD-9264/profile/8773/arrayexpressuploader012celllymphomaproteinsarcomaDec.12, 2014FalseE-GEOD-9264_A-AFFY-44transcription-profiling-of-human-primary-effusio-2Transcription profiling of human primary effusion lymphoma cell lines reveals Kaposis sarcoma-associated herpesvirus encodes an ortholog of miR-155Sep.22, 2014MicroRNAs are small, non-coding RNAs that post-transcriptionally regulate gene expression by binding to 3’UTRs of target mRNAs. Kaposi’s sarcoma-associated herpesvirus (KSHV), a virus linked to malignancies including primary effusion lymphoma (PEL), encodes 12 miRNA genes, but only a few regulatory targets are known. We found that KSHV-miR-K12-11 shares 100% seed-sequence homology with hsa-miR-155, a miRNA frequently found up-regulated in lymphomas and critically important for B cell development. Based on this seed-sequence homology, we hypothesized that both miRNAs regulate a common set of target genes and as a result, could have similar biological activities. Examination of five PEL lines showed that PELs do not express miR-155, but do express high levels of miR-K12-11. Bioinformatics tools predicted the transcriptional repressor BACH-1 to be targeted by both miRNAs and ectopic expression of either miR-155 or miR-K12-11 inhibited a BACH-1 3'UTR containing reporter. . Furthermore, BACH-1 protein levels are low in cells expressing either miRNA. Gene expression profiling of miRNA-expressing stable cell lines revealed 66 genes that were commonly down-regulated. For select genes, miRNA targeting was confirmed by reporter assays. Thus, based on our in silico predictions, reporter assays, and expression profiling data, miR-K12-11 and miR-155 regulate a common set of cellular targets. Given the role of miR-155 during B cell maturation, we speculate that miR-K12-11 may contribute to the distinct developmental phenotype of PEL cells, which are blocked in a late stage of B cell development. Together, these findings indicate that KSHV miR-K12-11 is an ortholog of miR-155. Experiment Overall Design: 12 samples, 4 experiemental (miR-155 ), 4 experimental (miR-K12-11) and 4 reference controls (pCDNA3.1)http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-9264humanhttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-9264/samples/