| Experiment ID | EXP00115 |
| Reference | Title: MicroRNA-375 targets AEG-1 in hepatocellular carcinoma and suppresses livercancer cell growth in vitro and in vivo. Author: He XX, Chang Y, Meng FY, Wang MY, Xie QH, Tang F, Li PY, Song YH, Lin JS. Journal: Oncogene. 2012 Jul 12;31(28):3357-69. doi: 10.1038/onc.2011.500. Epub 2011 Nov 7. Abstract: MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis andhave great potential for the diagnosis and treatment of cancer. However, theroles of miRNAs in hepatocellular carcinogenesis are still not fully elucidated. We investigated the aberrantly expressed miRNAs involved in hepatoma bycomparison of miRNA expression profiles in cancerous hepatocytes with normalprimary human hepatocytes, and 37 dysregulated miRNAs were screened out bytwofold change with a significant difference (P<0.05). Clustering analysis based on 13 miRNAs with changes over 15-folds showed that the miRNA expression patternsbetween the cancerous and normal hepatocytes were clearly different. Among the 13miRNAs, we found that miR-375 was significantly downregulated in hepatocellularcarcinoma (HCC) tissues and cell lines. Overexpression of miR-375 in liver cancercells decreased cell proliferation, clonogenicity, migration/invasion and alsoinduced G1 arrest and apoptosis. To unveil the molecular mechanism ofmiR-375-mediated phenotype in hepatoma cells described above, we examined theputative targets using bioinformatics tools and found that astrocyte elevatedgene-1 (AEG-1) was a potential target of miR-375. Then we demonstrated thatmiR-375 bound directly to the 3'-untranslated region of AEG-1 and inhibited theexpression of AEG-1. TaqMan quantitative reverse transcriptase-PCR and westernblot 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 tomiR-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 hepatomaxenografts in nude mice. In conclusion, our findings indicate that miR-375targets AEG-1 in HCC and suppresses liver cancer cell growth in vitro and invivo, and highlight the therapeutic potential of miR-375 in HCC treatment. PMID: 22056881 |
| Expressiion Profile | Description: Aberrantly microRNA profiling in cancerous hepatocytes versus normal primary hepatocytes Organism: Homo sapiens GEO ID: GSE20077 Platform: GPL8227 Number of samples: 11 |
| Design and Sample | Cancer Type: hepatocellular carcinoma Cancer SubType: N/D Cell Line: N/D Experimental Design: cancer vs normal Case Sample: cancerous hepatocytes Control Sample: normal primary hepatocytes Num of Case: 7 Num of Control: 3 Quantification Software: Limma Num of miRNAs: 723 |
| Identification | Num of Up: 1 Num of Down: 5 |