Global Regulation on microRNA in Hepatitis B Virus-Associated Hepatocellular Carcinoma

Abstract

Recent work has revealed the causative links between deregulation of microRNAs (miRNAs) and cancer development. In hepatocellular carcinoma (HCC), aberrant expression of miRNAs has been observed, but the molecular mechanisms that contribute to such changes remains to be elucidated. Here, we reported the analysis of miRNA expression in 94 pairs of tumor and adjacent nontumor tissues from HBV-associated HCC in Chinese patients. We found miRNAs were aberrantly expressed in HCC tissues. To investigate the cause of such deregulation, we detected changes in DNA copy number by measuring locus-specific hybridization intensity, and found changes in expression of several miRNAs are correlated with genomic amplification or deletion. For example, the genomic regions of miR-30d and miR-151 were amplified in ∼50% of HCC tumor tissues, and the expressions of these miRNAs are significantly correlated with DNA copy number. We also employed cDNA microarray data, and provide evidence that key regulators of the miRNA biosynthetic pathway, including DROSHA, DGCR8, AGO1, and AGO2, are frequently overexpressed in HCC. This study provides molecular clues that may contribute to the global changes of miRNA expression in HCC.

Argonaute, Dicer, and Drosha are up-regulated along tumor progression in serous ovarian carcinoma

“…Data regarding other types of cancer are similarly limited, particularly with respect to disease outcome. Differences in the expression of Ago1, Ago2, or both have been shown in comparative analysis of skin tumors to normal skin and in comparison between hepatocellular carcinoma and nontumor tissue in Chinese patients infected with the hepatitis B virus [19,20]. Somatic mutations in the Ago2 gene were recently found in gastric and colorectal carcinomas with high microsatellite instability [21], and Ago2 was frequently detected in colorectal carcinomas in an additional study [22].…”

Expression of the microRNA regulators Drosha, Dicer and Ago2 in non-small cell lung carcinomas

“…Recent studies have shown that perturbations of Ago2 may play a role in oncogenesis [8,21,[45][46][47]. Indeed, it has been reported that Ago2 is expressed in human colorectal and breast carcinomas at both the protein and mRNA levels, and that its expression has a tendency to be elevated in tumors of higher grades [21,48].…”

DLK1-DIO3 Genomic Imprinted MicroRNA Cluster at 14q32.2 Defines a Stemlike Subtype of Hepatocellular Carcinoma Associated with Poor Survival

“…Expression levels of 220 human miRNAs were measured by custom quantitative PCR assays, as described previously (15,16). Transcript expression levels were detected by microarray, as described previously (17,18).…”