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MicroRNA deregulation in HCV-associated hepatocellular carcinoma

Abstract number: O181

Sinigaglia A., Barzon L., Lavezzo E., Trevisan M., Farinati F., Palù G.

Objectives: Recent evidences on the role of microRNAs (miRNAs) in human cancers and their possible effects on HCV replication led us to investigate miRNAs expression profile in HCV-related hepatocellular carcinoma (HCC) as compared to adjacent non-neoplastic liver and its relationship with the presence of HCV infection.

Methods: Tissue samples from 22 HCCs and adjacent non-tumoral tissue were obtained from surgical specimens removed during HCC resection. RNA extraction from samples was performed using miRNA-compatible protocols and reagents. miRNAs expression profile was investigated by microarray analysis and confirmed by real-time RT-PCR. HCV detection and typing was performed by RT-PCR-sequencing by using PCR primer pairs targeting different regions of viral genome.

Results: HCV RNA was detected in 17 out of 22 HCCs; HCV genotype 1b accounted for 60% positive cases and HCV-1a and 2 for 20% each. Analysis of miRNA expression profile in HCCs showed deregulation of a group of miRNAs, including miR-122a, which was down-regulated in 15 (76%) cases as compared with non-neoplastic adjacent liver samples; miR-195, miR-199a, and miR-199b, which were consistently under-expressed in about 60% of HCCs, and miR-145, under-expressed in 40% of cases. At variance, miR-222 was up-regulated in 50% HCCs. MiR-145, miR-222, and miR-199a showed a stronger deregulation in HCV-positive HCCs than in HCV-negative cancers. These miRNAs could play an important role in the development of HCC since they target many genes involved in the control of cell cycle and cell proliferation, as predicted by the Sanger miRBASE Sequences Database. Among target genes, there are cyclin G1 (regulated by miR-122a), cyclin E1 (potentially regulated by miR-195), map3k4 and map3k11 (targeted by miR-199a and miR-199b, respectively), junB (targeted by miR-199b), bcl-w and cdc42 (targeted by miR-195), and ras-related protein rreb1 (targeted by miR-199a).

Conclusions: While investigating a larger number of HCC samples, these results indicate that HCC, and in particular HCV-related HCC, is characterised by deregulation of a set of miRNAs involved in the control of the cell cycle.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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