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Nrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma.

Zhang M, Zhang C, Zhang L, Yang Q, Zhou S, Wen Q, Wang J - BMC Cancer (2015)

Bottom Line: 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.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.Nrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma partly through regulating expression of Bcl-xL and MMP-9.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China. zmx3115@163.com.

ABSTRACT

Background: Nuclear 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.

Methods: First, 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.

Results: Nrf2 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.

Conclusion: Nrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma partly through regulating expression of Bcl-xL and MMP-9.

No MeSH data available.


Related in: MedlinePlus

Effect of Nrf2 on cell invasion in vitro.a Bel-7402 cells transfected with shRNA-Nrf2 (shRNA-1757 or shRNA-2019) or control shRNA (shNC) were subjected to transwell invasion assays; b The invasive cell numbers are the average count of five random microscopic fields detected using the transwell invasion assay; c HepG2 cells transfected with Nrf2 expression plasmid (pEFGP-Nrf2-1 or pEFGP-Nrf2-2) or mock pEGFP plasmid (pEGFP-NC) were subjected to transwell invasion assays; d The invasive cell numbers are the average count of five random microscopic fields detected using the transwell invasion assay. Each bar represents the mean ± SD of the counts. e After shRNA-Nrf2 (shRNA-1757 or shRNA-2019)) or control shRNA (shNC) transduction, expression of MMP-9 were detected by western blot in Bel-7402 cells; f After Nrf2 expression plasmid (pEFGP-Nrf2-1 or pEFGP-Nrf2-2) or mock pEGFP plasmid (pEGFP-NC) transduction, expression of MMP-9 were detected by western blot in HepG2 cells. *P < 0.05 compared with control (Bel-7402 cells or HepG2 cells respectively) or shNC and pEGFP-NC
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Fig5: Effect of Nrf2 on cell invasion in vitro.a Bel-7402 cells transfected with shRNA-Nrf2 (shRNA-1757 or shRNA-2019) or control shRNA (shNC) were subjected to transwell invasion assays; b The invasive cell numbers are the average count of five random microscopic fields detected using the transwell invasion assay; c HepG2 cells transfected with Nrf2 expression plasmid (pEFGP-Nrf2-1 or pEFGP-Nrf2-2) or mock pEGFP plasmid (pEGFP-NC) were subjected to transwell invasion assays; d The invasive cell numbers are the average count of five random microscopic fields detected using the transwell invasion assay. Each bar represents the mean ± SD of the counts. e After shRNA-Nrf2 (shRNA-1757 or shRNA-2019)) or control shRNA (shNC) transduction, expression of MMP-9 were detected by western blot in Bel-7402 cells; f After Nrf2 expression plasmid (pEFGP-Nrf2-1 or pEFGP-Nrf2-2) or mock pEGFP plasmid (pEGFP-NC) transduction, expression of MMP-9 were detected by western blot in HepG2 cells. *P < 0.05 compared with control (Bel-7402 cells or HepG2 cells respectively) or shNC and pEGFP-NC

Mentions: Because there was a correlation between Nrf2 and metastasis, a transwell assay was performed to investigate the role of Nrf2 on the invasion of HCC cells. Down-regulation of Nrf2 expression repressed the cell invasion ability of Bel-7402 cells, and up-regulation of Nrf2 expression promoted the cell invasion ability of HepG2 cells (P < 0.05, Fig. 5a to d). These findings suggest that Nrf2 regulates cell invasion of the HCC cell lines in vitro. We therefore assessed the expression of matrix metalloproteinases-9 (MMP-9), a protein regulating cell migration and invasion, in Bel-7402 cells transfected with shRNA-Nrf2 and HepG2 cells transected with pEGFP-Nrf2. Expression of MMP-9 was positively correlated with the expression of Nrf2: inhibition of Nrf2 decreased the MMP-9 expression while up-regulation of Nrf2 increased the MMP-9 expression (Fig. 5e to f).Fig. 5


Nrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma.

Zhang M, Zhang C, Zhang L, Yang Q, Zhou S, Wen Q, Wang J - BMC Cancer (2015)

Effect of Nrf2 on cell invasion in vitro.a Bel-7402 cells transfected with shRNA-Nrf2 (shRNA-1757 or shRNA-2019) or control shRNA (shNC) were subjected to transwell invasion assays; b The invasive cell numbers are the average count of five random microscopic fields detected using the transwell invasion assay; c HepG2 cells transfected with Nrf2 expression plasmid (pEFGP-Nrf2-1 or pEFGP-Nrf2-2) or mock pEGFP plasmid (pEGFP-NC) were subjected to transwell invasion assays; d The invasive cell numbers are the average count of five random microscopic fields detected using the transwell invasion assay. Each bar represents the mean ± SD of the counts. e After shRNA-Nrf2 (shRNA-1757 or shRNA-2019)) or control shRNA (shNC) transduction, expression of MMP-9 were detected by western blot in Bel-7402 cells; f After Nrf2 expression plasmid (pEFGP-Nrf2-1 or pEFGP-Nrf2-2) or mock pEGFP plasmid (pEGFP-NC) transduction, expression of MMP-9 were detected by western blot in HepG2 cells. *P < 0.05 compared with control (Bel-7402 cells or HepG2 cells respectively) or shNC and pEGFP-NC
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4507320&req=5

Fig5: Effect of Nrf2 on cell invasion in vitro.a Bel-7402 cells transfected with shRNA-Nrf2 (shRNA-1757 or shRNA-2019) or control shRNA (shNC) were subjected to transwell invasion assays; b The invasive cell numbers are the average count of five random microscopic fields detected using the transwell invasion assay; c HepG2 cells transfected with Nrf2 expression plasmid (pEFGP-Nrf2-1 or pEFGP-Nrf2-2) or mock pEGFP plasmid (pEGFP-NC) were subjected to transwell invasion assays; d The invasive cell numbers are the average count of five random microscopic fields detected using the transwell invasion assay. Each bar represents the mean ± SD of the counts. e After shRNA-Nrf2 (shRNA-1757 or shRNA-2019)) or control shRNA (shNC) transduction, expression of MMP-9 were detected by western blot in Bel-7402 cells; f After Nrf2 expression plasmid (pEFGP-Nrf2-1 or pEFGP-Nrf2-2) or mock pEGFP plasmid (pEGFP-NC) transduction, expression of MMP-9 were detected by western blot in HepG2 cells. *P < 0.05 compared with control (Bel-7402 cells or HepG2 cells respectively) or shNC and pEGFP-NC
Mentions: Because there was a correlation between Nrf2 and metastasis, a transwell assay was performed to investigate the role of Nrf2 on the invasion of HCC cells. Down-regulation of Nrf2 expression repressed the cell invasion ability of Bel-7402 cells, and up-regulation of Nrf2 expression promoted the cell invasion ability of HepG2 cells (P < 0.05, Fig. 5a to d). These findings suggest that Nrf2 regulates cell invasion of the HCC cell lines in vitro. We therefore assessed the expression of matrix metalloproteinases-9 (MMP-9), a protein regulating cell migration and invasion, in Bel-7402 cells transfected with shRNA-Nrf2 and HepG2 cells transected with pEGFP-Nrf2. Expression of MMP-9 was positively correlated with the expression of Nrf2: inhibition of Nrf2 decreased the MMP-9 expression while up-regulation of Nrf2 increased the MMP-9 expression (Fig. 5e to f).Fig. 5

Bottom Line: 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.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.Nrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma partly through regulating expression of Bcl-xL and MMP-9.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China. zmx3115@163.com.

ABSTRACT

Background: Nuclear 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.

Methods: First, 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.

Results: Nrf2 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.

Conclusion: Nrf2 is a potential prognostic marker and promotes proliferation and invasion in human hepatocellular carcinoma partly through regulating expression of Bcl-xL and MMP-9.

No MeSH data available.


Related in: MedlinePlus