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Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties

Oncogene volume 28, pages 3526–3536 (2009)Cite this article

Abstract

Growing evidence indicates that microRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. In this study, we evaluated the clinical and functional relevance of microRNA-122 (miR-122) expression in human hepatocellular carcinoma (HCC). We report that miR-122 is specifically repressed in a subset of primary tumors that are characterized by poor prognosis. We further show that the loss of miR-122 expression in tumor cells segregates with specific gene expression profiles linked to cancer progression, namely the suppression of hepatic phenotype and the acquisition of invasive properties. We identify liver-enriched transcription factors as central regulatory molecules in the gene networks associated with loss of miR-122, and provide evidence suggesting that miR-122 is under the transcriptional control of HNF1A, HNF3A and HNF3B. We further show that loss of miR-122 results in an increase of cell migration and invasion and that restoration of miR-122 reverses this phenotype. In conclusion, miR-122 is a marker of hepatocyte-specific differentiation and an important determinant in the control of cell migration and invasion. From a clinical point of view, our study emphasizes miR-122 as a diagnostic and prognostic marker for HCC progression.

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Accession codes

Accessions

GenBank/EMBL/DDBJ

Abbreviations

HCC:

hepatocellular carcinoma

miRNA:

microRNA

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Acknowledgements

This project was supported in part by the Intramural Research Program of the Center for Cancer Research.

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Authors and Affiliations

  1. Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    C Coulouarn, V M Factor, J B Andersen, M E Durkin & S S Thorgeirsson

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  1. C Coulouarn
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  2. V M Factor
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  3. J B Andersen
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Correspondence to S S Thorgeirsson.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Coulouarn, C., Factor, V., Andersen, J. et al. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene 28, 3526–3536 (2009). https://doi.org/10.1038/onc.2009.211

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