Elevated expression of the miR-17-92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype

Erin Connolly, Margherita Melegari, Pablo Landgraf, Tatyana Tchaikovskaya, Bud C. Tennant, Betty L. Slagle, Leslie E. Rogler, Mihaela Zavolan, Thomas Tuschl, Charles E. Rogler

Research output: Contribution to journalArticle

200 Scopus citations

Abstract

Alterations in microRNA (miRNA) expression in both human and animal models have been linked to many forms of cancer. Such miRNAs, which act directly as repressors of gene expression, have been found to frequently reside in fragile sites and genomic regions associated with cancer. This study describes a miRNA signature for human primary hepatitis B virus-positive human hepatocellular carcinoma. Moreover, two known oncomiRs - miRNAs with known roles in cancer - the miR-17-92 polycistron and miR-21, exhibited increased expression in 100% of primary human and woodchuck hepatocellular carcinomas surveyed. To determine the importance of these miRNAs in tumorigenesis, an in vitro antisense oligonucleotide knockdown model was evaluated for its ability to reverse the malignant phenotype. Both in human and woodchuck HCC cell lines, separate treatments with antisense oligonucleotides specific for either the miR-17-92 polycistron (all six members) or miR-21 caused a 50% reduction in both hepatocyte proliferation and anchorage-independent growth. The combination of assays presented here supports a role for these miRNAs in the maintenance of the malignant transformation of hepatocytes.

Original languageEnglish (US)
Pages (from-to)856-864
Number of pages9
JournalAmerican Journal of Pathology
Volume173
Issue number3
DOIs
StatePublished - Sep 2008

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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