Dysregulated microRNAs in non-cirrhotic hepatocellular carcinoma

Abstract

MicroRNAs (miRNAs) are endogenous non-coding 21-23 nucleotide RNAs that are involved in post-transcriptional regulation. They control various cellular processes, one of which is tumorigenesis. miRNAs have been implicated in the pathogenesis of hepatocellular carcinoma (HCC), the most common primary liver cancer. To find yet-to-be-identified miRNAs associated with HCC tumorigenesis, we resected HCC and adjacent non-tumor liver tissues from patients and excluded liver tissues harboring fibrosis from further analysis. We then carried out miRNA microarray analysis with miRNAs extracted from the tissues. Sixteen miRNAs displayed a significant change in expression levels between non-tumor and HCC liver tissues. To validate the microarray findings, we transfected HEK293 cells with miR-128 alone or miR-128 and plasmid encoding luciferase fused to the 3' untranslated region (UTR) of E2F3, a predicted target of miR-128. As expected, miR-128 downregulated luciferase activities of E2F3 3'UTR fused to luciferase, confirming that E2F3 is a target gene of miR-128. Identification of miRNAs dysregulated in non-cirrhotic HCC will further the understanding of the pathogenesis of non-cirrhotic HCC.