miR-483-3p and drug resistance in Hepatocarcinoma

Project Information

VEROMIRNA

Grant agreement ID: 303987

Project closed

Start date 1 October 2012

End date 30 September 2016

Funded under

• Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)

Total cost € 100 000,00

EU contribution € 100 000,00

Coordinated by

UNIVERSITA DEGLI STUDI GABRIELE D'ANNUNZIO DI CHIETI-PESCARA
Italy

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 (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.

• medical and health sciences › basic medicine › pharmacology and pharmacy › drug resistance
• medical and health sciences › clinical medicine › oncology

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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
• Region: Sud › Abruzzo › Chieti
• Activity type: Higher or Secondary Education Establishments
• Total cost: No data