Data from Cyclin G1 Is a Target of miR-122a, a MicroRNA Frequently Down-regulated in Human Hepatocellular Carcinoma

Abstract

<div>Abstract<p>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 <i>let-7</i> family, <i>mir-221,</i> and <i>mir-145</i>. In addition, the hepato-specific <i>miR-122a</i> was found down-regulated in ∼70% of HCCs and in all HCC-derived cell lines. Microarray data for <i>let-7a, mir-221,</i> and <i>mir-122a</i> 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 <i>miR-122a</i> can modulate cyclin G1 expression in HCC-derived cell lines and an inverse correlation between <i>miR-122a</i> and cyclin G1 expression exists in primary liver carcinomas. These results indicate that cyclin G1 is a target of <i>miR-122a</i> and expand our knowledge of the molecular alterations involved in HCC pathogenesis and of the role of miRNAs in human cancer. [Cancer Res 2007;67(13):6092–9]</p></div>