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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 is correlated with distant metastasis in HCCA, JARID1B protein expression was analyzed by immunohistochemical analysis in 178 cases HCC tissues and the representative results were shown. B, semiquantification of JARID1B expression in normal tissues, primary HCC tissues without or with distant metastasis. Normal, normal liver tissues; no distant met, primary cancers without distant metastasis (in situ); distant met, primary cancers with distant metastasis. **, P < 0.01 is based on the Student t test. Error bars, SD. C, the association between JARID1B expression in HCC and the survival time of selected patients was analyzed with Kaplan-Meier survival analysis. Scale bars, 50 μm (upper) and 20 μm (lower) in A.
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Figure 2: JARID1B is correlated with distant metastasis in HCCA, JARID1B protein expression was analyzed by immunohistochemical analysis in 178 cases HCC tissues and the representative results were shown. B, semiquantification of JARID1B expression in normal tissues, primary HCC tissues without or with distant metastasis. Normal, normal liver tissues; no distant met, primary cancers without distant metastasis (in situ); distant met, primary cancers with distant metastasis. **, P < 0.01 is based on the Student t test. Error bars, SD. C, the association between JARID1B expression in HCC and the survival time of selected patients was analyzed with Kaplan-Meier survival analysis. Scale bars, 50 μm (upper) and 20 μm (lower) in A.

Mentions: We examined JARID1B protein expression in more HCC samples by IHC (Figure 2A). We observed that the level of JARID1B positive cells was markedly higher in HCC tissues than the level in the normal liver tissues (Figure 2B). Most importantly, JARID1B overexpression was consistently significantly correlated to distant metastasis in these HCC samples (Figure 2B). To investigate the relationship between JARID1B expression and clinicopathological parameters in the 178 cases with HCCs, these cases were first divided into two subgroups: “low JARID1B expression” and “high JARID1B expression” as defined in the immunohistochemistry section of “Materials and methods”. Significant correlations were found between JARID1B expression and tumor diameter, microvascular invasion, and tumor differentiation. There were no statistical connections between JARID1B expression and the rest clinicopathological parameters, such as patient age, gender, and HBsAg (Table 1). The association between JARID1B expression in HCC and the survival time of selected patients was analyzed with Kaplan-Meier survival analysis (Figure 2C). The median overall survival time of high JARID1B expression group was significantly shorter than that of low JARID1B expression group (P < 0.001). These results collectively indicate a functional role of JARID1B in aggressive behaviors of HCCs.


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 is correlated with distant metastasis in HCCA, JARID1B protein expression was analyzed by immunohistochemical analysis in 178 cases HCC tissues and the representative results were shown. B, semiquantification of JARID1B expression in normal tissues, primary HCC tissues without or with distant metastasis. Normal, normal liver tissues; no distant met, primary cancers without distant metastasis (in situ); distant met, primary cancers with distant metastasis. **, P < 0.01 is based on the Student t test. Error bars, SD. C, the association between JARID1B expression in HCC and the survival time of selected patients was analyzed with Kaplan-Meier survival analysis. Scale bars, 50 μm (upper) and 20 μm (lower) in A.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: JARID1B is correlated with distant metastasis in HCCA, JARID1B protein expression was analyzed by immunohistochemical analysis in 178 cases HCC tissues and the representative results were shown. B, semiquantification of JARID1B expression in normal tissues, primary HCC tissues without or with distant metastasis. Normal, normal liver tissues; no distant met, primary cancers without distant metastasis (in situ); distant met, primary cancers with distant metastasis. **, P < 0.01 is based on the Student t test. Error bars, SD. C, the association between JARID1B expression in HCC and the survival time of selected patients was analyzed with Kaplan-Meier survival analysis. Scale bars, 50 μm (upper) and 20 μm (lower) in A.
Mentions: We examined JARID1B protein expression in more HCC samples by IHC (Figure 2A). We observed that the level of JARID1B positive cells was markedly higher in HCC tissues than the level in the normal liver tissues (Figure 2B). Most importantly, JARID1B overexpression was consistently significantly correlated to distant metastasis in these HCC samples (Figure 2B). To investigate the relationship between JARID1B expression and clinicopathological parameters in the 178 cases with HCCs, these cases were first divided into two subgroups: “low JARID1B expression” and “high JARID1B expression” as defined in the immunohistochemistry section of “Materials and methods”. Significant correlations were found between JARID1B expression and tumor diameter, microvascular invasion, and tumor differentiation. There were no statistical connections between JARID1B expression and the rest clinicopathological parameters, such as patient age, gender, and HBsAg (Table 1). The association between JARID1B expression in HCC and the survival time of selected patients was analyzed with Kaplan-Meier survival analysis (Figure 2C). The median overall survival time of high JARID1B expression group was significantly shorter than that of low JARID1B expression group (P < 0.001). These results collectively indicate a functional role of JARID1B in aggressive behaviors of HCCs.

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