272 MIR-338-3P IS DOWN-REGULATED BY HEPATITIS B VIRUS X AND INHIBITS CELL PROLIFERATION BY TARGETING CYCLIND1 MAINLY AT 2397-2403NT OF CYCLIND1 3 UTR

epithelial-to-mesenchymal transition (EMT), which converts it in a tumor promoter [2]. TGF-beta in culture induces apoptosisresistant hepatocytes to undergo EMT [3], coincident with the acquisition of stem cell properties [4]. The aim of this work was to assess and compare expression of well-known stem markers in hepatocellular carcinoma cell lines with different epithelial/mesenchymal phenotype and autocrine expression of TGF-beta. Methods: In vitro cell culture of HepG2, Hep3B, PLC-PRF-5, SNU449. In vivomodels of subcutaneous implanted Hep3B and HepG2 cells. Results: Using immunofluorescence and flow cytometry, we found closely inexistent expression of the stem-markers Thy-1 and c-Kit, but we identified a noteworthy pattern for EpCAM and CD44 in differently aggressive cell lines. This expression patterns were also found in tumor samples obtained from xenografts by immunohistochemistry. CD44 expression, a marker linked to metastatic spreading [5] was only present in Snu449 cell line, which showed, among the used lines, the highest TGF-beta expression levels and the most mesenchymal profile, concordant with a late TGF-beta signature [6]. Pericellular EpCAM was found in all other cell lines, coincident with a more epithelial phenotype and an early TGF-beta signature. No expression was found in Snu449 cells. Although EpCAM is missing in differentiated hepatocytes, its presence in progenitor cells during regeneration is linked to a hepatic lineage commitment process. Furthermore, its cleavage is necessary for its stem-related gene promotion [7]. Conclusion: CD44/EpCAM phenotype is an interesting trait to look for in HCC, in order to correlate its presence with a dedifferentiated and invasive phenotype. Acknowledgements: Grants: MCINN, Spain (BFU2009-07219 and ISCIII-RTICC: RD06/0020) and AGAUR-Generalitat de Catalunya (2009SGR-312). ISCIII-RTICC “Short-stay” grant was fundamental for cooperating with University of Extremadura.