MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer
Authors: Kalpana Ghoshal
Samson T Jacob
Roger Henson
Fanyin Meng
Tushar Patel
Hania Wehbe-Janek
Journal: Gastroenterology (2007)
Discipline: CLINICAL MEDICINE
Keywords: microRNAs; miR-21; hepatocellular cancer; HCC; gene expression
Affiliations: Department of Internal Medicine, Scott and White Clinic, Texas A&M University System Health Science Center College of Medicine, Temple, Texas, USA.

Abstract:  Background and 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. 

Retracted: No

PubPeer comments:
  Figure 2 miR-21 is up-regulated in human primary HCC. Total RNA was isolated from HCC (t) and matching control (n), and Northern blot analysis was performed as described in the Materials and Methods section. The signal in each lane was quantified by Kodak Imaging software and the ratio of miR-21 to 5S ribosomal RNA was determined. Asterisks denote human primary HCC in which mir-21 is up-regulated. In the first 9 samples the signal is higher because more RNA (20 u03bcg) was loaded. For samples 10u201320, 10 u03bcg of RNA was loaded. The loading control band for samples 10 to 16, when darkened and rescaled, is very hard to distinguish from the band for samples 1 to 7. ![file] Why the vertical discontinuities around the miR-21 lanes for sample 18? , 
 Figure 9A. PTEN band is spliced in the middle. Other bands are not spliced. ![file] , 
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