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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 tumorigenesis and metastasis in vivoA and D, representative images of HepG2-pBabe-JARID1B (A), SK-Hep1-pSuper-shJARID1B (D) or their control cell tumors by subcutaneous injection. B and E, growth curve of tumors formed by HepG2-pBabe-JARID1B (B), SK-Hep1-pSuper-shJARID1B (E) or their control cells by subcutaneous injection. C and F, the weight of tumors formed by HepG2-pBabe-JARID1B (C), SK-Hep1-pSuper-shJARID1B (F) or their control cells at harvest time. G, the total numbers of mice with distant metastasis at 60 days after injection of HepG2-pBabe-JARID1B, SK-Hep1-pSuper-shJARID1B or their control cells. H and I, the numbers of metastatic foci per section in lung of individual mouse with injection of HepG2-pBabe-JARID1B (H), SK-Hep1-pSuper-shJARID1B (I) or their control cells. n=5 for subcutaneous transplantation and n=5 for tail vein injection. **, 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 6: JARID1B promotes tumorigenesis and metastasis in vivoA and D, representative images of HepG2-pBabe-JARID1B (A), SK-Hep1-pSuper-shJARID1B (D) or their control cell tumors by subcutaneous injection. B and E, growth curve of tumors formed by HepG2-pBabe-JARID1B (B), SK-Hep1-pSuper-shJARID1B (E) or their control cells by subcutaneous injection. C and F, the weight of tumors formed by HepG2-pBabe-JARID1B (C), SK-Hep1-pSuper-shJARID1B (F) or their control cells at harvest time. G, the total numbers of mice with distant metastasis at 60 days after injection of HepG2-pBabe-JARID1B, SK-Hep1-pSuper-shJARID1B or their control cells. H and I, the numbers of metastatic foci per section in lung of individual mouse with injection of HepG2-pBabe-JARID1B (H), SK-Hep1-pSuper-shJARID1B (I) or their control cells. n=5 for subcutaneous transplantation and n=5 for tail vein injection. **, P < 0.01 is based on the Student t test. All results are from three independent experiments. Error bars, SD.

Mentions: To extend our in vitro observations, we investigated whether JARID1B could regulate tumorigenic and metastatic capacity of HCC cells in vivo. HepG2-pBabe-JARID1B, SK-Hep1-pSuper-shJARID1B and their corresponding control cells were subcutaneously injected into nude mice. Tumor size was measured every week up to 6 weeks. As expected, the tumors from HepG2-pBabe-JARID1B cells grew more rapidly at the implantation site than the control cells (Figure 6A - C). In contrast, silencing JARID1B in the typically aggressive SK-Hep1 cells led to a dramatic decrease in tumor volume and weight (Figure 6D - F).


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 tumorigenesis and metastasis in vivoA and D, representative images of HepG2-pBabe-JARID1B (A), SK-Hep1-pSuper-shJARID1B (D) or their control cell tumors by subcutaneous injection. B and E, growth curve of tumors formed by HepG2-pBabe-JARID1B (B), SK-Hep1-pSuper-shJARID1B (E) or their control cells by subcutaneous injection. C and F, the weight of tumors formed by HepG2-pBabe-JARID1B (C), SK-Hep1-pSuper-shJARID1B (F) or their control cells at harvest time. G, the total numbers of mice with distant metastasis at 60 days after injection of HepG2-pBabe-JARID1B, SK-Hep1-pSuper-shJARID1B or their control cells. H and I, the numbers of metastatic foci per section in lung of individual mouse with injection of HepG2-pBabe-JARID1B (H), SK-Hep1-pSuper-shJARID1B (I) or their control cells. n=5 for subcutaneous transplantation and n=5 for tail vein injection. **, P < 0.01 is based on the Student t test. All results are from three independent experiments. Error bars, SD.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: JARID1B promotes tumorigenesis and metastasis in vivoA and D, representative images of HepG2-pBabe-JARID1B (A), SK-Hep1-pSuper-shJARID1B (D) or their control cell tumors by subcutaneous injection. B and E, growth curve of tumors formed by HepG2-pBabe-JARID1B (B), SK-Hep1-pSuper-shJARID1B (E) or their control cells by subcutaneous injection. C and F, the weight of tumors formed by HepG2-pBabe-JARID1B (C), SK-Hep1-pSuper-shJARID1B (F) or their control cells at harvest time. G, the total numbers of mice with distant metastasis at 60 days after injection of HepG2-pBabe-JARID1B, SK-Hep1-pSuper-shJARID1B or their control cells. H and I, the numbers of metastatic foci per section in lung of individual mouse with injection of HepG2-pBabe-JARID1B (H), SK-Hep1-pSuper-shJARID1B (I) or their control cells. n=5 for subcutaneous transplantation and n=5 for tail vein injection. **, P < 0.01 is based on the Student t test. All results are from three independent experiments. Error bars, SD.
Mentions: To extend our in vitro observations, we investigated whether JARID1B could regulate tumorigenic and metastatic capacity of HCC cells in vivo. HepG2-pBabe-JARID1B, SK-Hep1-pSuper-shJARID1B and their corresponding control cells were subcutaneously injected into nude mice. Tumor size was measured every week up to 6 weeks. As expected, the tumors from HepG2-pBabe-JARID1B cells grew more rapidly at the implantation site than the control cells (Figure 6A - C). In contrast, silencing JARID1B in the typically aggressive SK-Hep1 cells led to a dramatic decrease in tumor volume and weight (Figure 6D - F).

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