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 L. Tchaikovskaya, Bud C. Tennant, Betty L. Slagle, Leslie E. Rogler, Mihaela Zavolan, Thomas Tuschl, Charles E. Rogler

Research output: Contribution to journalArticle

193 Citations (Scopus)

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

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Hepadnaviridae
MicroRNAs
Hepatocellular Carcinoma
Phenotype
Marmota
Antisense Oligonucleotides
Hepatocytes
Neoplasms
Hepatitis B virus
Carcinogenesis
Animal Models
Maintenance
Gene Expression
Cell Line
Growth

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Elevated expression of the miR-17-92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype. / Connolly, Erin; Melegari, Margherita; Landgraf, Pablo; Tchaikovskaya, Tatyana L.; Tennant, Bud C.; Slagle, Betty L.; Rogler, Leslie E.; Zavolan, Mihaela; Tuschl, Thomas; Rogler, Charles E.

In: American Journal of Pathology, Vol. 173, No. 3, 09.2008, p. 856-864.

Research output: Contribution to journalArticle

Connolly, Erin ; Melegari, Margherita ; Landgraf, Pablo ; Tchaikovskaya, Tatyana L. ; Tennant, Bud C. ; Slagle, Betty L. ; Rogler, Leslie E. ; Zavolan, Mihaela ; Tuschl, Thomas ; Rogler, Charles E. / Elevated expression of the miR-17-92 polycistron and miR-21 in hepadnavirus-associated hepatocellular carcinoma contributes to the malignant phenotype. In: American Journal of Pathology. 2008 ; Vol. 173, No. 3. pp. 856-864.
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