Cyclin G1 is a target of miR-122a, a microRNA frequently down-regulated in human hepatocellular carcinoma.
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.
Gramantieri
Laura
L
Dipartimento di Medicina Interna e Gastroenterologia e Centro di Ricerca Biomedica Applicata, Università di Bologna, Bologna, Italy.
Ferracin
Manuela
M
Fornari
Francesca
F
Veronese
Angelo
A
Sabbioni
Silvia
S
Liu
Chang-Gong
CG
Calin
George A
GA
Giovannini
Catia
C
Ferrazzi
Eros
E
Grazi
Gian Luca
GL
Croce
Carlo M
CM
Bolondi
Luigi
L
Negrini
Massimo
M
D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology; D045744:Cell Line, Tumor; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016174:Hepacivirus / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics*; D014162:Transfection
C534702:CCNG1 protein, human; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins; D035683:MicroRNAs; D012334:RNA, Neoplasm; C487931:mirnlet7 microRNA, human