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Open Access Research article

The expression level of miR-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis

Yoshiki Murakami1*, Akihiro Tamori1, Saori Itami1, Toshihito Tanahashi2, Hidenori Toyoda3, Masami Tanaka47, Weihong Wu4, Nariso Brojigin4, Yuji Kaneoka5, Atsuyuki Maeda5, Takashi Kumada3, Norifumi Kawada1, Shoji Kubo6 and Masahiko Kuroda4

Author Affiliations

1 Department of Hepatology, Graduate School of Medicine Osaka City University, Osaka, 545-8585, Japan

2 Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan

3 Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, 503-8502, Japan

4 Department of Molecular Pathology, Tokyo Medical University, Tokyo, 160-8402, Japan

5 Department of Surgery, Ogaki Municipal Hospital, Ogaki, 503-8502, Japan

6 Department of Hepato-Biliary-Pancreatic Surgery, Graduate School of Medicine, Osaka City University, Osaka, 545-8585, Japan

7 Present address: Laboratory of Genome Technology, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, 108-8679, Japan

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BMC Cancer 2013, 13:99  doi:10.1186/1471-2407-13-99

Published: 4 March 2013

Abstract

Background

Many studies support the hypothesis that specific microRNA (miRNA) expression in various human cancers including hepatocarcinogenesis is closely associated with diagnosis and prognosis. In hepatocellular carcinoma (HCC), malignancy level is related to the degree of histological differentiation.

Methods

In order to establish a novel biomarker that can determine the degree of malignancy and forecast patient prognosis, we performed a microarray analysis to investigate the miRNA expression profiles in 110 HCC which were comprised of 60 moderately, 30 poorly, and 20 well differentiated HCC.

Results

We found that the expression of 12 miRNAs varied significantly according to the degree of histological differentiation. Particularly, miR-18b expression in poorly differentiated HCC was significantly higher than in well differentiated HCC. Based on miRanda and Targetscan target search algorithms and Argonaute 2 immunoprecipitation study, we noted that miR-18b can control the expression of trinucleotide repeat containing 6B (TNRC6B) as a target gene. Additionally, in two hepatoma cell lines, we found that over-expression of miR-18b or down-regulation of TNRC6B accelerated cell proliferation and loss of cell adhesion ability. Finally, we observed that after surgical resection, HCC patients with high miR-18b expression had a significantly shorter relapse-free period than those with low expression.

Conclusions

miR-18b expression is an important marker of cell proliferation and cell adhesion, and is predictive of clinical outcome. From a clinical point of view, our study emphasizes miR-18b as a diagnostic and prognostic marker for HCC progression.

Keywords:
Hepatocellular carcinoma; Histological differentiation; miRNA; Biomarker; TNRC6B