Cyclin G1 is a target of miR-122a, a MicroRNA frequently down-regulated in human hepatocellular carcinoma

Laura Gramantieri, Manuela Ferracin, Francesca Fornari, Angelo Veronese, Silvia Sabbioni, Chang Gong Liu, George A. Calin, Catia Giovannini, Eros Ferrazzi, Gian Luca Grazi, Carlo M. Croce, Luigi Bolondi, Massimo Negrini

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Abstract

We investigated the role of microRNAs (miRNAs) in the pathogenesis of human hepatocellular carcinoma (HCC). A genome-wide miRNA microarray was used to identify differentially expressed miRNAs in HCCs arisen on cirrhotic livers. Thirty-five miRNAs were identified. Several of these miRNAs were previously found deregulated in other human cancers, such as members of the let-7 family, mir-221, and mir-145. In addition, the hepato-specific miR-122a was found down-regulated in ∼70% of HCCs and in all HCC-derived cell lines. Microarray data for let-7a, mir-221, and mir-122a were validated by Northern blot and real-time PCR analysis. Understanding the contribution of deregulated miRNAs to cancer requires the identification of gene targets. Here, we show that miR-122a can modulate cyclin G1 expression in HCC-derived cell lines and an inverse correlation between miR-122a and cyclin G1 expression exists in primary liver carcinomas. These results indicate that cyclin G1 is a target of miR-122a and expand our knowledge of the molecular alterations involved in HCC pathogenesis and of the role of miRNAs in human cancer.

Original languageEnglish
Pages (from-to)6092-6099
Number of pages8
JournalCancer Research
Volume67
Issue number13
DOIs
Publication statusPublished - Jul 1 2007

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gramantieri, L., Ferracin, M., Fornari, F., Veronese, A., Sabbioni, S., Liu, C. G., Calin, G. A., Giovannini, C., Ferrazzi, E., Grazi, G. L., Croce, C. M., Bolondi, L., & Negrini, M. (2007). Cyclin G1 is a target of miR-122a, a MicroRNA frequently down-regulated in human hepatocellular carcinoma. Cancer Research, 67(13), 6092-6099. https://doi.org/10.1158/0008-5472.CAN-06-4607