Premium
Up‐regulated microRNA‐143 transcribed by nuclear factor kappa B enhances hepatocarcinoma metastasis by repressing fibronectin expression
Author(s) -
Zhang Xiaoying,
Liu Shanrong,
Hu Tingsong,
Liu Shupeng,
He Ying,
Sun Shuhan
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23008
Subject(s) - hbx , metastasis , microrna , cancer research , hepatitis b virus , hepatocellular carcinoma , cancer , biology , medicine , immunology , virus , gene , biochemistry
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‐κB) 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‐κB 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. (H EPATOLOGY 2009.)