MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis and 
have great potential for the diagnosis and treatment of cancer. However, the 
roles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated. 
We investigated the aberrantly expressed miRNAs involved in hepatoma by 
comparison of miRNA expression profiles in cancerous hepatocytes with normal 
primary human hepatocytes, and 37 dysregulated miRNAs were screened out by 
twofold change with a significant difference (P<0.05). Clustering analysis based 
on 13 miRNAs with changes over 15-folds showed that the miRNA expression 
patterns between the cancerous and normal hepatocytes were clearly different. 
Among the 13 miRNAs, we found that miR-375 was significantly downregulated in 
hepatocellular carcinoma (HCC) tissues and cell lines. Overexpression of miR-375 
in liver cancer cells decreased cell proliferation, clonogenicity, 
migration/invasion and also induced G1 arrest and apoptosis. To unveil the 
molecular mechanism of miR-375-mediated phenotype in hepatoma cells described 
above, we examined the putative targets using bioinformatics tools and found 
that astrocyte elevated gene-1 (AEG-1) was a potential target of miR-375. Then 
we demonstrated that miR-375 bound directly to the 3'-untranslated region of 
AEG-1 and inhibited the expression of AEG-1. TaqMan quantitative reverse 
transcriptase-PCR and western blot analysis showed that miR-375 expression was 
inversely correlated with AEG-1 expression in HCC tissues. Knockdown of AEG-1 by 
RNAi in HCC cells, similar to miR-375 overexpression, suppressed tumor 
properties. Ectopic expression of AEG-1, conversely, could partially reverse the 
antitumor effects of miR-375. In a mouse model, therapeutic administration of 
cholesterol-conjugated 2'-O-methyl-modified miR-375 mimics (Chol-miR-375) could 
significantly suppress the growth of hepatoma xenografts in nude mice. In 
conclusion, our findings indicate that miR-375 targets AEG-1 in HCC and 
suppresses liver cancer cell growth in vitro and in vivo, and highlight the 
therapeutic potential of miR-375 in HCC treatment.