Format

Send to

Choose Destination
Hepatology. 2009 Aug;50(2):490-9. doi: 10.1002/hep.23008.

Up-regulated microRNA-143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression.

Author information

1
Department of Medical Genetics, Second Military Medical University, Shanghai, PR China.

Abstract

It is increasingly clear that hepatocellular carcinoma (HCC) has a distinct microRNA (miRNA) expression profile that is involved in malignancy; however, little is known about how functional miRNA modulates the metastasis of hepatitis B virus (HBV)-related HCC (HBV-HCC). In the present study, we demonstrate that the levels of miRNA-143 (miR-143) are dramatically increased in metastatic HBV-HCC of both p21-HBx transgenic mice and HCC patients. Moreover, we show that overexpression of this miRNA is transcribed by nuclear factor kappa B (NF-kappaB) and favors liver tumor cell invasive and metastatic behavior. Intratumoral administration of miR-143 shows that high levels of miR-143 can significantly promote HCC metastasis in an athymic nude mouse model. An in vivo study that used p21-HBx transgenic mice also showed that local liver metastasis and distant lung metastasis are significantly inhibited by blocking miR-143. Additionally, fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as the direct and functional target of miR-143 both in vivo and in vitro.

CONCLUSION:

Up-regulation of miR-143 expression transcribed by NF-kappaB in HBV-HCC promotes cancer cell invasion/migration and tumor metastasis by repression of FNDC3B expression. The present study provides a better understanding of the specificity of the biological behavior and thus may be helpful in developing an effective treatment against HBV-HCC.

PMID:
19472311
DOI:
10.1002/hep.23008
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center