Gramantieri Laura, Ferracin Manuela, Fornari Francesca, Veronese Angelo, Sabbioni Silvia, Liu Chang-Gong, Calin George A, Giovannini Catia, Ferrazzi Eros, Grazi Gian Luca, Croce Carlo M, Bolondi Luigi, Negrini Massimo
Dipartimento di Medicina Interna e Gastroenterologia e Centro di Ricerca Biomedica Applicata, Università di Bologna, Bologna, Italy.
Cancer Res. 2007 Jul 1;67(13):6092-9. doi: 10.1158/0008-5472.CAN-06-4607.
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 approximately 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.
我们研究了微小RNA（miRNA）在人类肝细胞癌（HCC）发病机制中的作用。利用全基因组miRNA微阵列来鉴定在肝硬化肝脏上发生的HCC中差异表达的miRNA。共鉴定出35种miRNA。其中几种miRNA先前在其他人类癌症中被发现失调，如let-7家族成员、mir-221和mir-145。此外，肝脏特异性miR-122a在约70%的HCC以及所有HCC衍生细胞系中被发现下调。let-7a、mir-221和mir-122a的微阵列数据通过Northern印迹和实时PCR分析进行了验证。要了解失调的miRNA对癌症的作用，需要鉴定基因靶点。在此，我们表明miR-122a可调节HCC衍生细胞系中细胞周期蛋白G1的表达，并且在原发性肝癌中miR-122a与细胞周期蛋白G1表达之间存在负相关。这些结果表明细胞周期蛋白G1是miR-122a的一个靶点，并扩展了我们对HCC发病机制中涉及的分子改变以及miRNA在人类癌症中的作用的认识。
