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JARID1B promotes metastasis and epithelial-mesenchymal transition via PTEN/AKT signaling in hepatocellular carcinoma cells.

Tang B, Qi G, Tang F, Yuan S, Wang Z, Liang X, Li B, Yu S, Liu J, Huang Q, Wei Y, Zhai R, Lei B, Yu H, Jiao X, He S - Oncotarget (2015)

Bottom Line: In addition Kaplan-Meier survival analysis showed that high expression of JARID1B was associated with decreased overall survival of HCC patients.Mechanistically, we found JARID1B exerts its function through modulation of H3K4me3 at the PTEN gene promoter, which was associated with inactive PTEN transcription.Our results, for the first time, portray a pivotal role of JARID1B in stimulating metastatic behaviors of HCC cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.

ABSTRACT
JARID1B is a member of the family of JmjC domain-containing proteins that removes methyl residues from methylated lysine 4 on histone H3 lysine 4 (H3K4). JARID1B has been proposed as an oncogene in many types of tumors; however, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unknown. Here we show that JARID1B is elevated in HCC and its expression level is positively correlated with metastasis. In addition Kaplan-Meier survival analysis showed that high expression of JARID1B was associated with decreased overall survival of HCC patients. Overexpression of JARID1B in HCC cells increased proliferation, epithelial-mesenchymal transition, migration and invasion in vitro, and enhanced tumorigenic and metastatic capacities in vivo. In contrast, silencing JARID1B in aggressive and invasive HCC cells inhibited these processes. Mechanistically, we found JARID1B exerts its function through modulation of H3K4me3 at the PTEN gene promoter, which was associated with inactive PTEN transcription. PTEN overexpression blocked JARID1B-driven proliferation, EMT, and metastasis. Our results, for the first time, portray a pivotal role of JARID1B in stimulating metastatic behaviors of HCC cells. Targeting JARID1B may thus be a useful strategy to impede HCC cell invasion and metastasis.

No MeSH data available.


Related in: MedlinePlus

JARID1B regulates the transition between epithelial and mesenchymal phenotypes in HCC cellsA, representative phase-contrast images of Huh-7 and HepG2 cells showed JARID1B overexpression-modulated morphologic changes. B, expression of epithelial and mesenchymal marker was analyzed by immunofluorescence stains in Huh-7 and HepG2 cells. C, expression of epithelial and mesenchymal marker was analyzed by Western blotting in Huh-7 and HepG2 cells. D, representative phase-contrast images of SNU423 and SK-Hep1 cells showed JARID1B knockdown-modulated morphologic changes. E, expression of epithelial and mesenchymal marker was analyzed by immunofluorescence stains in SNU423 and SK-Hep1 cells. F, expression of epithelial and mesenchymal marker was analyzed by Western blotting in SNU423 and SK-Hep1 cells.
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Figure 4: JARID1B regulates the transition between epithelial and mesenchymal phenotypes in HCC cellsA, representative phase-contrast images of Huh-7 and HepG2 cells showed JARID1B overexpression-modulated morphologic changes. B, expression of epithelial and mesenchymal marker was analyzed by immunofluorescence stains in Huh-7 and HepG2 cells. C, expression of epithelial and mesenchymal marker was analyzed by Western blotting in Huh-7 and HepG2 cells. D, representative phase-contrast images of SNU423 and SK-Hep1 cells showed JARID1B knockdown-modulated morphologic changes. E, expression of epithelial and mesenchymal marker was analyzed by immunofluorescence stains in SNU423 and SK-Hep1 cells. F, expression of epithelial and mesenchymal marker was analyzed by Western blotting in SNU423 and SK-Hep1 cells.

Mentions: To investigate whether JARID1B positively regulates cell migration and invasion, we first observed the morphological changes and found that both Huh7-pBabe-JARID1B and HepG2-pBabe-JARID1B cells exhibited fibroblastic morphology (Figure 4A). This observation was further confirmed by expression analyses of epithelial and mesenchymal markers. We showed that JARID1B overexpression decreased the levels of epithelial markers (E-cadherin and α-catenin) and increased the levels of mesenchymal markers (N-cadherin and vimentin) in both cell lines (Figure 4B and 4C). Conversely, both SNU423-pSuper-shJARID1B and SK-Hep1-pSuper-shJARID1B cells reverted to an epithelial phenotype as compared to their respective control cells (Figure 4D). Consistent with this, silencing JARID1B increased levels of epithelial markers, and decreased levels of mesenchymal markers (Figure 4E and 4F). Taken together, these findings suggest that JARID1B plays an important role in regulating EMT-MET plasticity of HCC cells.


JARID1B promotes metastasis and epithelial-mesenchymal transition via PTEN/AKT signaling in hepatocellular carcinoma cells.

Tang B, Qi G, Tang F, Yuan S, Wang Z, Liang X, Li B, Yu S, Liu J, Huang Q, Wei Y, Zhai R, Lei B, Yu H, Jiao X, He S - Oncotarget (2015)

JARID1B regulates the transition between epithelial and mesenchymal phenotypes in HCC cellsA, representative phase-contrast images of Huh-7 and HepG2 cells showed JARID1B overexpression-modulated morphologic changes. B, expression of epithelial and mesenchymal marker was analyzed by immunofluorescence stains in Huh-7 and HepG2 cells. C, expression of epithelial and mesenchymal marker was analyzed by Western blotting in Huh-7 and HepG2 cells. D, representative phase-contrast images of SNU423 and SK-Hep1 cells showed JARID1B knockdown-modulated morphologic changes. E, expression of epithelial and mesenchymal marker was analyzed by immunofluorescence stains in SNU423 and SK-Hep1 cells. F, expression of epithelial and mesenchymal marker was analyzed by Western blotting in SNU423 and SK-Hep1 cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494969&req=5

Figure 4: JARID1B regulates the transition between epithelial and mesenchymal phenotypes in HCC cellsA, representative phase-contrast images of Huh-7 and HepG2 cells showed JARID1B overexpression-modulated morphologic changes. B, expression of epithelial and mesenchymal marker was analyzed by immunofluorescence stains in Huh-7 and HepG2 cells. C, expression of epithelial and mesenchymal marker was analyzed by Western blotting in Huh-7 and HepG2 cells. D, representative phase-contrast images of SNU423 and SK-Hep1 cells showed JARID1B knockdown-modulated morphologic changes. E, expression of epithelial and mesenchymal marker was analyzed by immunofluorescence stains in SNU423 and SK-Hep1 cells. F, expression of epithelial and mesenchymal marker was analyzed by Western blotting in SNU423 and SK-Hep1 cells.
Mentions: To investigate whether JARID1B positively regulates cell migration and invasion, we first observed the morphological changes and found that both Huh7-pBabe-JARID1B and HepG2-pBabe-JARID1B cells exhibited fibroblastic morphology (Figure 4A). This observation was further confirmed by expression analyses of epithelial and mesenchymal markers. We showed that JARID1B overexpression decreased the levels of epithelial markers (E-cadherin and α-catenin) and increased the levels of mesenchymal markers (N-cadherin and vimentin) in both cell lines (Figure 4B and 4C). Conversely, both SNU423-pSuper-shJARID1B and SK-Hep1-pSuper-shJARID1B cells reverted to an epithelial phenotype as compared to their respective control cells (Figure 4D). Consistent with this, silencing JARID1B increased levels of epithelial markers, and decreased levels of mesenchymal markers (Figure 4E and 4F). Taken together, these findings suggest that JARID1B plays an important role in regulating EMT-MET plasticity of HCC cells.

Bottom Line: In addition Kaplan-Meier survival analysis showed that high expression of JARID1B was associated with decreased overall survival of HCC patients.Mechanistically, we found JARID1B exerts its function through modulation of H3K4me3 at the PTEN gene promoter, which was associated with inactive PTEN transcription.Our results, for the first time, portray a pivotal role of JARID1B in stimulating metastatic behaviors of HCC cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People's Republic of China.

ABSTRACT
JARID1B is a member of the family of JmjC domain-containing proteins that removes methyl residues from methylated lysine 4 on histone H3 lysine 4 (H3K4). JARID1B has been proposed as an oncogene in many types of tumors; however, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unknown. Here we show that JARID1B is elevated in HCC and its expression level is positively correlated with metastasis. In addition Kaplan-Meier survival analysis showed that high expression of JARID1B was associated with decreased overall survival of HCC patients. Overexpression of JARID1B in HCC cells increased proliferation, epithelial-mesenchymal transition, migration and invasion in vitro, and enhanced tumorigenic and metastatic capacities in vivo. In contrast, silencing JARID1B in aggressive and invasive HCC cells inhibited these processes. Mechanistically, we found JARID1B exerts its function through modulation of H3K4me3 at the PTEN gene promoter, which was associated with inactive PTEN transcription. PTEN overexpression blocked JARID1B-driven proliferation, EMT, and metastasis. Our results, for the first time, portray a pivotal role of JARID1B in stimulating metastatic behaviors of HCC cells. Targeting JARID1B may thus be a useful strategy to impede HCC cell invasion and metastasis.

No MeSH data available.


Related in: MedlinePlus