In hepatocellular carcinoma miR‐519d is up‐regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2

• DOI: 10.1002/path.3995
• Publication Date: 2012-01-19T15:23:32Z
• Authors: Francesca Fornari; Maddalena Milazzo; Pasquale Chieco; Massimo Negrini; Elena Marasco; Giovanni Capranico; Vilma Mantovani; Jessica Marinello; Silvia Sabbioni; Elisa Callegari; Matteo Cescon; Matteo Ravaioli; Carlo M Croce; Luigi Bolondi; Laura Gramantieri
• Keywords: Aged, 80 and over; Cyclin-Dependent Kinase Inhibitor p21; Male; Chromatin Immunoprecipitation; 0303 health sciences; Antibiotics, Antineoplastic; Carcinoma, Hepatocellular; Cell Cycle; Liver Neoplasms; microRNA, C19MC, HCC, methylation, CDKN1A/p21, PTEN, AKT3, TIMP2; Apoptosis; Hep G2 Cells; DNA Methylation; Middle Aged; Gene Expression Regulation, Neoplastic; MicroRNAs; 03 medical and health sciences; Cell Movement; Doxorubicin; Humans; Female; HEPATOCELLULAR CARCINOMA; Aged; Cell Proliferation

MiR-519d belongs to the chromosome 19 miRNA cluster (C19MC), largest human cluster. One of its members, miR-519d, is over-expressed in hepatocellular carcinoma (HCC) and we characterized contribution hepatocarcinogenesis. In HCC cells, over-expression miR-519d promotes cell proliferation, invasion impairs apoptosis following anticancer treatments. These functions are, at least part, exerted through direct targeting CDKN1A/p21, PTEN, AKT3 TIMP2. The mechanisms underlying aberrant expression were assayed by genomic DNA amplification, methylation analysis ChIP assay. hypomethylation C19MC TP53 respectively identified as an epigenetic change allowing one factors able activate transcription. conclusion, assessed oncogenic role characterizing biological functions, including modulation response treatments identifying TIMP2 among targets.