Cyclin g1 is a target of miR-122a, a MicroRNA frequently down-regulated in human hepatocellular carcinoma
Cyclin g1 is a target of miR-122a, a MicroRNA frequently down-regulated in human hepatocellular carcinoma
复制标题
DOI：
10.1158/0008-5472.can-06-4607
复制
发表时间：
2007-07-01
期刊：
影响因子：
11.2
通讯作者：
Negrini, Massimo
中科院分区：
文献类型：
--
作者：
Gramantieri, Laura;Ferracin, Manuela;Negrini, Massimo
我们研究了microRNAs （miRNAs）在人肝细胞癌（HCC）发病机制中的作用。一个全基因组miRNA微阵列被用来鉴定肝硬化肝上出现的hcc中差异表达的miRNA。共鉴定出35个mirna。这些mirna中的一些先前在其他人类癌症中被发现不受调控，例如let-7家族成员、mir-221和mir-145。此外，肝特异性miR-122a在大约70%的hcc和所有hcc衍生细胞系中被下调。通过Northern blot和real-time PCR分析验证let-7a、mir-221和mir-122a的芯片数据。了解不受调控的miPNAs对癌症的贡献需要确定基因靶标。在这里，我们发现miR-122a可以调节hcc来源细胞系中cyclin G1的表达，并且在原发性肝癌中miR-122a与cyclin G1的表达存在负相关。这些结果表明，细胞周期蛋白G1是miR-122a的靶标，并扩大了我们对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。
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 similar to 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 miPNAs 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.