Abstract
BackgroundNuclear factor E2-related factor 2 (Nrf2 or NFE2L2) is abundantly expressed in cancer cells and relates to proliferation, invasion, and chemoresistance. Our early observations also found that expression of Nrf2 was up-regulated in kinds of cancer including human hepatocellular carcinoma (HCC) cells. But there are limited reports about the expression, significance, function of Nrf2 in HCC.MethodsFirst, Nrf2 expression was analyzed in HCC cell lines and tumor samples. Then, the relationship of Nrf2 with clinicopathological factors and survival were analyzed. Further, the effect of Nrf2 on cell proliferation, apoptosis, and metastasis was examined in vitro by modulating expression of Nrf2 through specific shRNA or expression plasmid. Last, the potential mechanisms were also investigated.ResultsNrf2 was up-regulated in HCC, and expression of Nrf2 was correlated with tumor differentiation, metastasis, and tumor size. Univariate and multivariate analyses indicated that high Nrf2 expression might be a poor prognostic factor. Further studies demonstrated that inhibition of Nrf2 expression inhibited proliferation by inducing apoptosis and repressed invasion, and up-regulation of Nrf2 expression resulted in opposite phenotypes. Moreover, there are positive correlation between Nrf2 expression and that of Bcl-xL and MMP-9.ConclusionNrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma partly through regulating expression of Bcl-xL and MMP-9.
Highlights
Nuclear factor E2-related factor 2 (Nrf2 or NFE2L2) is abundantly expressed in cancer cells and relates to proliferation, invasion, and chemoresistance
We investigated whether the expression levels of Nrf2 correlate with malignant behaviors of hepatocellular carcinoma (HCC) including proliferation, apoptosis, and invasion through modulation of Nrf2 expression by RNA interference and expression plasmid
We will carry out in vivo experiments further to confirm the role of Nrf2 and its target genes in HCC. In conclusion, this was the first study to systemically evaluate the oncogenic functions of the Nrf2 in HCC
Summary
Nuclear factor E2-related factor 2 (Nrf or NFE2L2) is abundantly expressed in cancer cells and relates to proliferation, invasion, and chemoresistance. Our early observations found that expression of Nrf was up-regulated in kinds of cancer including human hepatocellular carcinoma (HCC) cells. There are limited reports about the expression, significance, function of Nrf in HCC. Multiple risk factors have been associated with the initiation and development of HCC, including chronic infection of Nuclear factor E2-related factor 2 (Nrf or NFE2L2) is a key transcription regulator for antioxidant and detoxification enzymes [6]. Many kinds of Nrf target genes are expressed in the liver. Nrf plays protective roles in hepatic inflammation, fibrosis, hepatocarcinogenesis, and regeneration via its target gene induction [9].
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