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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 promotes migratory and invasive capacities of HCC cells in vitroHuh7-pBabe-JARID1B (A), HepG2-pBabe-JARID1B (B) and theirs control vector cells were subjected to wound healing assays; the uncovered areas in the wound healing assays were quantified as a percentage of the original wound area. Huh7-pBabe-JARID1B (C), HepG2-pBabe-JARID1B (D) and theirs control vector cells were subjected to Transwell migration (C and D, top), and Matrigel invasion assays (C and D, bottom), quantification of migrated cells through the membrane and invaded cells through Matrigel of each cell line are shown as proportions of their vector controls. SNU423-pSuper-shJARID1B (E), SK-Hep1-pSuper-shJARID1B (F) and theirs control vector cells were subjected to wound healing assays, the uncovered areas in the wound healing assays were quantified as a percentage of the original wound area. SNU423-pSuper-shJARID1B (G), SK-Hep1-pSuper-shJARID1B (H) and theirs control vector cells were subjected to Transwell migration (G and H, top), and Matrigel invasion assays (G and H, bottom), quantification of migrated cells through the membrane and invaded cells through Matrigel of each cell line are shown as proportions of their vector controls. **, P < 0.01 is based on the Student t test. All results are from three independent experiments. Error bars, SD.
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Figure 5: JARID1B promotes migratory and invasive capacities of HCC cells in vitroHuh7-pBabe-JARID1B (A), HepG2-pBabe-JARID1B (B) and theirs control vector cells were subjected to wound healing assays; the uncovered areas in the wound healing assays were quantified as a percentage of the original wound area. Huh7-pBabe-JARID1B (C), HepG2-pBabe-JARID1B (D) and theirs control vector cells were subjected to Transwell migration (C and D, top), and Matrigel invasion assays (C and D, bottom), quantification of migrated cells through the membrane and invaded cells through Matrigel of each cell line are shown as proportions of their vector controls. SNU423-pSuper-shJARID1B (E), SK-Hep1-pSuper-shJARID1B (F) and theirs control vector cells were subjected to wound healing assays, the uncovered areas in the wound healing assays were quantified as a percentage of the original wound area. SNU423-pSuper-shJARID1B (G), SK-Hep1-pSuper-shJARID1B (H) and theirs control vector cells were subjected to Transwell migration (G and H, top), and Matrigel invasion assays (G and H, bottom), quantification of migrated cells through the membrane and invaded cells through Matrigel of each cell line are shown as proportions of their vector controls. **, P < 0.01 is based on the Student t test. All results are from three independent experiments. Error bars, SD.

Mentions: The effect of JARID1B on cell migration was first assessed by wound healing assay. Both Huh7-pBabe-JARID1B and HepG2-pBabe-JARID1B cells had significantly faster closure of the wound area compared to their control cells (Figure 5A and 5B). This result was confirmed by Boyden's chamber assay (Figure 5C and 5D). Moreover, Huh7-pBabe-JARID1B and HepG2-pBabe-JARID1B cells showed a greater degree of invasion through Matrigel (Figure 5C and 5D). In contrast, silencing JARID1B dramatically reduced the migratory and invasive capacity of SNU423 and SK-Hep1 cells (Figure 5E - H), suggesting that restoration of an epithelial phenotype through MET may dampen or inhibit their mobility potential. These results indicate that JARID1B promotes migratory and invasive behaviors in 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 promotes migratory and invasive capacities of HCC cells in vitroHuh7-pBabe-JARID1B (A), HepG2-pBabe-JARID1B (B) and theirs control vector cells were subjected to wound healing assays; the uncovered areas in the wound healing assays were quantified as a percentage of the original wound area. Huh7-pBabe-JARID1B (C), HepG2-pBabe-JARID1B (D) and theirs control vector cells were subjected to Transwell migration (C and D, top), and Matrigel invasion assays (C and D, bottom), quantification of migrated cells through the membrane and invaded cells through Matrigel of each cell line are shown as proportions of their vector controls. SNU423-pSuper-shJARID1B (E), SK-Hep1-pSuper-shJARID1B (F) and theirs control vector cells were subjected to wound healing assays, the uncovered areas in the wound healing assays were quantified as a percentage of the original wound area. SNU423-pSuper-shJARID1B (G), SK-Hep1-pSuper-shJARID1B (H) and theirs control vector cells were subjected to Transwell migration (G and H, top), and Matrigel invasion assays (G and H, bottom), quantification of migrated cells through the membrane and invaded cells through Matrigel of each cell line are shown as proportions of their vector controls. **, P < 0.01 is based on the Student t test. All results are from three independent experiments. Error bars, SD.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4494969&req=5

Figure 5: JARID1B promotes migratory and invasive capacities of HCC cells in vitroHuh7-pBabe-JARID1B (A), HepG2-pBabe-JARID1B (B) and theirs control vector cells were subjected to wound healing assays; the uncovered areas in the wound healing assays were quantified as a percentage of the original wound area. Huh7-pBabe-JARID1B (C), HepG2-pBabe-JARID1B (D) and theirs control vector cells were subjected to Transwell migration (C and D, top), and Matrigel invasion assays (C and D, bottom), quantification of migrated cells through the membrane and invaded cells through Matrigel of each cell line are shown as proportions of their vector controls. SNU423-pSuper-shJARID1B (E), SK-Hep1-pSuper-shJARID1B (F) and theirs control vector cells were subjected to wound healing assays, the uncovered areas in the wound healing assays were quantified as a percentage of the original wound area. SNU423-pSuper-shJARID1B (G), SK-Hep1-pSuper-shJARID1B (H) and theirs control vector cells were subjected to Transwell migration (G and H, top), and Matrigel invasion assays (G and H, bottom), quantification of migrated cells through the membrane and invaded cells through Matrigel of each cell line are shown as proportions of their vector controls. **, P < 0.01 is based on the Student t test. All results are from three independent experiments. Error bars, SD.
Mentions: The effect of JARID1B on cell migration was first assessed by wound healing assay. Both Huh7-pBabe-JARID1B and HepG2-pBabe-JARID1B cells had significantly faster closure of the wound area compared to their control cells (Figure 5A and 5B). This result was confirmed by Boyden's chamber assay (Figure 5C and 5D). Moreover, Huh7-pBabe-JARID1B and HepG2-pBabe-JARID1B cells showed a greater degree of invasion through Matrigel (Figure 5C and 5D). In contrast, silencing JARID1B dramatically reduced the migratory and invasive capacity of SNU423 and SK-Hep1 cells (Figure 5E - H), suggesting that restoration of an epithelial phenotype through MET may dampen or inhibit their mobility potential. These results indicate that JARID1B promotes migratory and invasive behaviors in 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