Objective Hsa-mir-483 is located within intron 2 of the INS-IGF2 gene. We have previously shown oncogenic features of miR-483-3p targeting the pro-apoptotic gene BBC3/PUMA (P53 up-regulated modulator of apoptosis gene) giving drug resistance to cells. Generally the IGF2 and miR-483 expression are strictly correlated although we have demonstrated that expression of miR-483 can be induced independently of IGF2 by the oncoprotein b-catenin. In Hepatocarcinoma (HCC) IGF2/483 locus is often over-expressed probably by Loss of Imprinting (LOI) at the IGF2/H19 imprinted control region (ICR) and HepG2 and Hep3B HCC cell lines shown the entire IGF2/483 locus up-regulated. As a matter of fact we found that the treatment with the de-methylating agent 5-azacytidine, induces an important down-regulation of IGF2 and miR-483-3p genes.Moreover, during the course of our study we found that the chemotherapeutic drug 5-fluoruracyl (5-FU) induces increased expression of miR-483-3p in HepG2 and Hep3B cells. 5-FU treatment does not affect all the HCC cell lines that we tested suggesting a possible heterogeneity in cellular drug resistance dependently from miR-483-3p induced expression. Aim of this project is to investigate the mechanism involved in the 5-FU/miR-483 regulation, identify its importance in chemotherapeutic resistance in HCC primary tissues and explore if a concomitant treatment with the de-methylating agent 5-azacytidine and chemotherapeutic 5-FU, could improve the susceptibility to apoptosis of cancer cells. Fields of science medical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemedical and health sciencesclinical medicineoncology Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants" Call for proposal FP7-PEOPLE-2011-CIG See other projects for this call Funding Scheme MC-CIG - Support for training and career development of researcher (CIG) Coordinator UNIVERSITA DEGLI STUDI GABRIELE D'ANNUNZIO DI CHIETI-PESCARA EU contribution € 100 000,00 Address Via dei Vestini 31 66013 Chieti Italy See on map Region Sud Abruzzo Chieti Activity type Higher or Secondary Education Establishments Administrative Contact Elvira D' Annunzio (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data