MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer

Fanyin Meng, Roger Henson, Hania Wehbe-Janek, Kalpana Ghoshal, Samson T. Jacob, Tushar C Patel

Research output: Contribution to journalArticle

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Abstract

Background & Aims: microRNAs (miRNAs) are short noncoding RNAs that regulate gene expression negatively. Although a role for aberrant miRNA expression in cancer has been postulated, the pathophysiologic role and relevance of aberrantly expressed miRNA to tumor biology has not been established. Methods: We evaluated the expression of miRNA in human hepatocellular cancer (HCC) by expression profiling, and defined a target gene and biologically functional effect of an up-regulated miRNA. Results: miR-21 was noted to be highly overexpressed in HCC tumors and cell lines in expression profiling studies using a miRNA microarray. Inhibition of miR-21 in cultured HCC cells increased expression of the phosphatase and tensin homolog (PTEN) tumor suppressor, and decreased tumor cell proliferation, migration, and invasion. In contrast-enhanced miR-21 expression by transfection with precursor miR-21 increased tumor cell proliferation, migration, and invasion. Moreover, an increase in cell migration was observed in normal human hepatocytes transfected with precursor miR-21. PTEN was shown to be a direct target of miR-21, and to contribute to miR-21 effects on cell invasion. Modulation of miR-21 altered focal adhesion kinase phosphorylation and expression of matrix metalloproteases 2 and 9, both downstream mediators of PTEN involved in cell migration and invasion. Conclusions: Aberrant expression of miR-21 can contribute to HCC growth and spread by modulating PTEN expression and PTEN-dependent pathways involved in mediating phenotypic characteristics of cancer cells such as cell growth, migration, and invasion.

Original languageEnglish (US)
Pages (from-to)647-658
Number of pages12
JournalGastroenterology
Volume133
Issue number2
DOIs
StatePublished - Aug 2007
Externally publishedYes

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Liver Neoplasms
Tumor Suppressor Genes
MicroRNAs
Phosphoric Monoester Hydrolases
Cell Movement
Neoplasms
Cell Proliferation
Small Untranslated RNA
Focal Adhesion Protein-Tyrosine Kinases
Metalloproteases
Growth
Tumor Cell Line
Transfection
Tensins
Hepatocytes
Phosphorylation
Gene Expression
Genes

ASJC Scopus subject areas

  • Gastroenterology

Cite this

MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer. / Meng, Fanyin; Henson, Roger; Wehbe-Janek, Hania; Ghoshal, Kalpana; Jacob, Samson T.; Patel, Tushar C.

In: Gastroenterology, Vol. 133, No. 2, 08.2007, p. 647-658.

Research output: Contribution to journalArticle

Meng, Fanyin ; Henson, Roger ; Wehbe-Janek, Hania ; Ghoshal, Kalpana ; Jacob, Samson T. ; Patel, Tushar C. / MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer. In: Gastroenterology. 2007 ; Vol. 133, No. 2. pp. 647-658.
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