Methods. MiR-26b expression was measured using real-time PCR in formalin-fixed paraffin-embedded tissue (FFPE) from 71 DLBCL cases (35 HCV+, 36 HCV-) and 10 controls (non-tumorous tonsils). MiR-26b was overexpressed in DLBCL- and control cell-lines by lentiviral transduction and

effects on cell growth, proliferation and apoptosis were studied. Also in vivo, influence of miR-26b expression on growth of subcutaneously transplanted tumors in NO D-SCID mice was monitored. Moreover, we studied a transgenic mouse model that putatively expresses the full HCV genome in B cells. Results. We found significantly downregulated expression of miR-26b in DLBCL of HCV-positive patients compared to HCVnegative DLBCL and controls (p = 0.0005 and p = 0.01, respectively). Native DLBCL cell lines (HCV-) showed 5 to 20-fold downregulation of miR-26b expression in comparison Acalabrutinib clinical trial to germinal center B-cells. Lentiviral overexpression in two DLBCL cell lines but Pritelivir cell line not in control B-cell lines led to increased growth and proliferation. Moreover, sub-cutaneous tumor growth in NODSCID mice was increased in miR-26b overexpressing cells compared to mock transduction (1.18g vs. 0.54 g, p = 0.01). HCV-expressing mice developed B-cell lymphomas, mainly DLBCL,

within 600 days in approximately a quarter of the transgenic mice. Again, miR-26b expression was downregulated in HCV-positive DLBCL tissue in comparison to HCV-negative lymphomas or non-tumorous controls (p = 0.0001

and p = 0.01, respectively). Conclusions. MiR-26b, a miRNA with known tumor suppressive potential, is downregulated in HCV-positive DLBCL. Furthermore, we could demonstrate in vitro and in vivo that miR-26b may mediate HCV-induced lymphomagenesis. Understanding of the molecular mechanisms of viral oncogenesis is an 上海皓元医药股份有限公司 important basis for the development of potential new treatment strategies. Disclosures: Stefan Zeuzem – Consulting: Abbvie, Achillion Pharmaceuticals, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Co., Gilead, Novartis Pharmaceuticals, Merck & Co., Idenix, Janssen, Roche Pharma AG, Vertex Pharmaceuticals, Presidio, Santaris, Inc The following people have nothing to disclose: Jan Peveling-Oberhag, Benjamin Rengstl, Frederic C. Chatain, Kyoko Tsukiyama-Kohara, Marco Lucioni, Marco Paulli, Martin Leo Hansmann Background: Veterans in Department of Veterans Affairs (VA) care are known to be at increased risk of hepatitis C virus (HCV) infection. In 2012, the Centers for Disease Control and Prevention (CDC) recommended one-time HCV screening for all persons born during 1945-1965 to reduce HCV-related morbidity and mortality. We assessed the extent to which Veterans, particularly those born during 1945-1965, have been screened for HCV and estimated the potential clinical impact of complete birth cohort screening based on HCV infection prevalence in those most recently screened.