In our study, all miR-223-positive cases of EN-NK/T-NT showed EBV

In our study, all miR-223-positive cases of EN-NK/T-NT showed EBV infection, implying that EBV infection may be responsible for miR-223 overexpression. Indeed, the upregulation of miR-223 has been observed after EBV transformation of lymphoblastoid cells [41]. Motsch et al. [42] also demonstrated that EBV exerts a profound find more effect on the cellular miRNA profile in EBV-positive NK/T-cell lymphomas compared to non-infected cases. Other reports have revealed that CCAAT/enhancer binding protein alpha and nuclear factor I/A regulate mature miR-223 by competing for a regulatory binding site 700 bp Pritelivir in vitro upstream of the pre-miR-223

sequence [43]. Thus, the mechanisms that regulate the level of miR-223 remain to be elucidated. Conclusions Collectively, these findings in our study indicate that PRDM1 is downregulated in EN-NK/T-NT cases and that PRDM1-positive staining may have prognostic value for evaluating the prognosis for EN-NK/T-NT patients. In addition, PRDM1 is likely to be a target of miR-223, and the overexpression of miR-223 might be an important genetic mechanism of PRDM1 downregulation in EN-NK/T-NT. miR-223-mediated silencing

of PRDM1 provides new insight into the genetic mechanisms underlying EN-NK/T-NT and an opportunity to identify new therapeutic strategies for EN-NK/T-NT. Acknowledgement This work was supported by the research grant 81071944 from National Natural Sciences Foundation of GSK458 nmr China, Beijing. References 1. Aozasa K, Takakuwa T, Hongyo T, Yang WI: Nasal NK/T-cell lymphoma: epidemiology and pathogenesis. Int J Hematol 2008, 87:110–117.PubMedCentralPubMedCrossRef 2. Ren YL, Nong L, Zhang S, Zhao J, Zhang XM, Li T: Analysis of 142 Northern Chinese patients with peripheral T/NK-Cell lymphomas: subtype distribution, clinicopathologic features, and prognosis. Am J Clin Pathol 2012, 138:435–447.PubMedCrossRef 3. Huang Y, de Reynies A, de Leval L, Ghazi

B, Martin-Garcia N, Travert M, Bosq J, Briere J, Petit B, Thomas E, et al.: Gene expression profiling identifies emerging oncogenic pathways operating in extranodal NK/T-cell lymphoma, nasal type. Blood 2010, 115:1226–1237.PubMedCrossRef 4. Coppo P, Gouilleux-Gruart V, Huang Y, Bouhlal H, Bouamar H, Bouchet S, Perrot C, Vieillard V, Dartigues P, Gaulard Methamphetamine P, et al.: STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma. Leukemia 2009, 23:1667–1678.PubMedCentralPubMedCrossRef 5. Zhang S, Li T, Zhang B, Nong L, Aozasa K: Transcription factors engaged in development of NK cells are commonly expressed in nasal NK/T-cell lymphomas. Hum Pathol 2011, 42:1319–1328.PubMedCrossRef 6. Yamanaka Y, Tagawa H, Takahashi N, Watanabe A, Guo YM, Iwamoto K, Yamashita J, Saitoh H, Kameoka Y, Shimizu N, et al.: Aberrant overexpression of microRNAs activate AKT signaling via down-regulation of tumor suppressors in natural killer-cell lymphoma/leukemia. Blood 2009, 114:3265–3275.PubMedCrossRef 7.

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