down-regulated in both tumour entities as compared to thymus. The down-regulation of miR-424 was essentially confirmed by qRT-PCR in the NK/Tcell lines and tumor tissue. We had previously detected also a down-regulation of miR-424 in prostate carcinoma. MiR-424 was linked to breast cancer as it PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22203832 is part of an oestrogen-responsive gene network in breast carcinoma cell lines. The down-regulation of miR-142-5p and miR-142-3p in the EBV-positive NK/T-cell lymphomas as compared to the EBV-negative lymphomas was also confirmed by the qRT-PCR analysis including a comparison between CD56+ primary cells and the NK/T-cell lines and the tumor tissues. Ng et al. also found a strong down-regulation of this miRNA. A computational search yielded the mRNA of the interleukin 1 alpha gene as a potential target for this miRNA. Concomitant with the decrease in miR142-3p, the mRNA levels for IL1A were up-regulated in EBV-positive lymphomas and we could indeed prove that the IL1A 39-UTR contains a binding site for this miRNA. Accordingly, miR-142 negatively regulated a reporter construct featuring the IL1A-39-UTR which lost its responsiveness upon binding site mutation. Lastly, we could demonstrate that miR-142, when ectopically expressed in a human cell line, reduced the protein levels of IL1A and also reduced the levels of secreted IL1A. The up-regulation of IL1A was previously MiRNA Profile of EBV-Positive NK/T-Cell Lymphoma 7 MiRNA Profile of EBV-Positive NK/T-Cell Lymphoma shown in EBV-positive NK/T-cell lymphomas along with mRNAs of other genes thought to be involved in cell proliferation such as BCL6 or ERBB4. The up-regulation of IL1A in 
the EBVpositive as compared to the EBV-negative lymphomas might be explained by the ability of the pro-inflammatory cytokine to act as an auto- or paracrine growth factor and as an inhibitor of apoptosis. Besides, this cytokine is known to be induced yet in several tumours, e.g. in NPCs, and to have tumour promoting activity. Except for the direct regulation of IL1A by miR-142-3p found in this study, the miRNA has also an indirect influence on IL1A. It was already reported that AC9 is regulated by miR-142-3p and that the inhibition of AC9 resulted in a reduced amount of cAMP. As cAMP in turn is able to induce the amount of IL1A, miR-142-3p is able to influence IL1A indirectly by regulating AC9, too. We show that IL1A is a target for miR-142-3p and that the down-regulation of this miRNA might confer a selective advantage to the EBV-infected cell by elevating IL1A levels. As mentioned, the BCL6 mRNA was also up-regulated in NK/ T-cell lymphomas. It should be pointed out that other studies did not find a deregulation of either IL1A or BCL6. A computational analysis indicated the BCL6-39-UTR as a potential target amongst others for miR-205 which was found here to be down-regulated in the EBV-positive NK/T-cell lymphomas and the EBV-negative samples as compared to order BIBW2992 normal tissue. The coexpression of miR-205 with a reporter construct featuring the BCL6-39-UTR showed that this 39-UTR is a target for miR-205; mutation of the binding site led to non-responsiveness of the reporter. Furthermore, ectopic expression of miR-205 resulted in down-regulation of the BCL6-protein level. BCL6 was originally discovered in B-cell lymphomas due to chromosomal translocations or mutations affecting this gene. More recently, BCL6 was also found to play a role in the development of T-cell lymphomas. The BCL6 oncogene is a transcriptional repress
