Cel 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. Dziedzina nauki medical and health sciencesbasic medicinepharmacology and pharmacydrug resistancemedical and health sciencesclinical medicineoncology Program(-y) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Temat(-y) FP7-PEOPLE-2011-CIG - Marie-Curie Action: "Career Integration Grants" Zaproszenie do składania wniosków FP7-PEOPLE-2011-CIG Zobacz inne projekty w ramach tego zaproszenia System finansowania MC-CIG - Support for training and career development of researcher (CIG) Koordynator UNIVERSITA DEGLI STUDI GABRIELE D'ANNUNZIO DI CHIETI-PESCARA Wkład UE € 100 000,00 Adres Via dei Vestini 31 66013 Chieti Włochy Zobacz na mapie Region Sud Abruzzo Chieti Rodzaj działalności Higher or Secondary Education Establishments Kontakt administracyjny Elvira D' Annunzio (Ms.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
