Cyclin g1 is a target of miR-122a, a MicroRNA frequently down-regulated in human hepatocellular carcinoma

被引:691
作者
Gramantieri, Laura
Ferracin, Manuela
Fornari, Francesca
Veronese, Airtgelo
Sabbioni, Silvia
Liu, Chang-Gong
Calin, George A.
Giovannini, Catia
Ferrazzi, Eros
Grazi, Gian Luca
Croce, Carlo M.
Bolondi, Luigi
Negrini, Massimo
机构
[1] Univ Bologna, Dipartimento Med Interna & Gastroenterol, I-40126 Bologna, Italy
[2] Univ Bologna, Ctr Ricerca Biomed Apolicata, I-40126 Bologna, Italy
[3] Univ Ferrara, Deipartimeno Med Sperimentale & Diagnost, I-44100 Ferrara, Italy
[4] Univ Ferrara, Comprehens Canc Ctr, I-44100 Ferrara, Italy
[5] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH USA
[6] Ist Oncol Veneto, Rovigo, Italy
关键词
D O I
10.1158/0008-5472.CAN-06-4607
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
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页码:6092 / 6099
页数:8
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