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The suppressive role of SOX7 in hepatocarcinogenesis.

Wang C, Guo Y, Wang J, Min Z - PLoS ONE (2014)

Bottom Line: We found HCC samples exhibited lower levels of SOX7 mRNA and protein expression than non-tumor samples, and the expression of SOX7 was negatively correlated with tumor size.SOX7 expression was also reduced in four HCC cell lines (SMMC-7721, Hep3B, HepG2 and Huh 7).The expression of Ki-67, a proliferation marker, was also reduced in SOX7-overexpression tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiamen, Fujian, China.

ABSTRACT
SOX7 is a transcription factor mediating various developmental processes. However, its role in hepatocellular carcinoma (HCC) remains unclear. Here, we assessed the role of SOX7 in hepatocarcinogenesis. We found HCC samples exhibited lower levels of SOX7 mRNA and protein expression than non-tumor samples, and the expression of SOX7 was negatively correlated with tumor size. SOX7 expression was also reduced in four HCC cell lines (SMMC-7721, Hep3B, HepG2 and Huh 7). Overexpression of SOX7 could inhibit HCC cell growth, with G1to S phase arrest. In SOX7-overexpression cells, cyclin D1 and c-myc, two cell cycle promoters, were down-regulated. Moreover, ectopic expression of cyclin D1 or c-myc could override G1 to S pahse arrest induced by SOX7. Furthermore, overexpression of SOX7 suppressed tumor formation with down-regulation of cyclin D1 and c-myc in vivo. The expression of Ki-67, a proliferation marker, was also reduced in SOX7-overexpression tumors. Taken together, our study suggests that SOX7 plays an important inhibitory role in hepatocarcinogenesis, and might be a novel target for HCC therapy.

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SOX7 induced G1 to S phase arrest by down-regulation of cyclin D1 and c-myc.(A) Western blotting analysis of SOX7, cyclin D1, c-myc and GAPDH levels in SMMC-7721 and Hep3B cells transfected with vector or SOX7. (B, C) Overexpression of cyclin D1 and c-myc could override G1 to S pahse arrest induced by SOX7. Cyclin D1 or c-myc was overexpressed in SOX7-overexpression cells, and the cell percentages in G0/G1, S and G2/M phase were measured by flow cytometric analysis. * indicates p<0.05. The experiments were performed independently three times at least.
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pone-0097433-g004: SOX7 induced G1 to S phase arrest by down-regulation of cyclin D1 and c-myc.(A) Western blotting analysis of SOX7, cyclin D1, c-myc and GAPDH levels in SMMC-7721 and Hep3B cells transfected with vector or SOX7. (B, C) Overexpression of cyclin D1 and c-myc could override G1 to S pahse arrest induced by SOX7. Cyclin D1 or c-myc was overexpressed in SOX7-overexpression cells, and the cell percentages in G0/G1, S and G2/M phase were measured by flow cytometric analysis. * indicates p<0.05. The experiments were performed independently three times at least.

Mentions: Since SOX7 could inhibit HCC cell growth, we further investigated the mechanism that mediated the anti-proliferation function. Flow cytometry was performed to examine the effects of SOX7 on cell cycle. We found overexpression of SOX7 increased the percentage of cells in G0/G1 peak but decreased that in S peak (Fig. 3), indicating that SOX7 could induce G1 to S phase arrest. Accordingly, we tested the expression of a panel of proteins involved in cell cycle. SOX7 overexpression had no effect on the expression of CDK4, and CDK6. However, the expression of two cell cycle promoters, cyclin D1 and c-myc, were down-regulated (Fig. 4A). Furthermore, to determine if cyclin D1 and c-my function downstream of SOX7, we overexpressed ectopic cyclin D1 or c-myc in SOX7-overexpression cells and examined the cell cycle. It is found that either cyclin D1 or c-myc overexpression could override the G1 to S pahse arrest induced by SOX7 (Fig. 4B, 4C). These data suggested SOX7 induced G1 to S phase arrest by down-regulation of cyclin D1 and c-myc.


The suppressive role of SOX7 in hepatocarcinogenesis.

Wang C, Guo Y, Wang J, Min Z - PLoS ONE (2014)

SOX7 induced G1 to S phase arrest by down-regulation of cyclin D1 and c-myc.(A) Western blotting analysis of SOX7, cyclin D1, c-myc and GAPDH levels in SMMC-7721 and Hep3B cells transfected with vector or SOX7. (B, C) Overexpression of cyclin D1 and c-myc could override G1 to S pahse arrest induced by SOX7. Cyclin D1 or c-myc was overexpressed in SOX7-overexpression cells, and the cell percentages in G0/G1, S and G2/M phase were measured by flow cytometric analysis. * indicates p<0.05. The experiments were performed independently three times at least.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4016311&req=5

pone-0097433-g004: SOX7 induced G1 to S phase arrest by down-regulation of cyclin D1 and c-myc.(A) Western blotting analysis of SOX7, cyclin D1, c-myc and GAPDH levels in SMMC-7721 and Hep3B cells transfected with vector or SOX7. (B, C) Overexpression of cyclin D1 and c-myc could override G1 to S pahse arrest induced by SOX7. Cyclin D1 or c-myc was overexpressed in SOX7-overexpression cells, and the cell percentages in G0/G1, S and G2/M phase were measured by flow cytometric analysis. * indicates p<0.05. The experiments were performed independently three times at least.
Mentions: Since SOX7 could inhibit HCC cell growth, we further investigated the mechanism that mediated the anti-proliferation function. Flow cytometry was performed to examine the effects of SOX7 on cell cycle. We found overexpression of SOX7 increased the percentage of cells in G0/G1 peak but decreased that in S peak (Fig. 3), indicating that SOX7 could induce G1 to S phase arrest. Accordingly, we tested the expression of a panel of proteins involved in cell cycle. SOX7 overexpression had no effect on the expression of CDK4, and CDK6. However, the expression of two cell cycle promoters, cyclin D1 and c-myc, were down-regulated (Fig. 4A). Furthermore, to determine if cyclin D1 and c-my function downstream of SOX7, we overexpressed ectopic cyclin D1 or c-myc in SOX7-overexpression cells and examined the cell cycle. It is found that either cyclin D1 or c-myc overexpression could override the G1 to S pahse arrest induced by SOX7 (Fig. 4B, 4C). These data suggested SOX7 induced G1 to S phase arrest by down-regulation of cyclin D1 and c-myc.

Bottom Line: We found HCC samples exhibited lower levels of SOX7 mRNA and protein expression than non-tumor samples, and the expression of SOX7 was negatively correlated with tumor size.SOX7 expression was also reduced in four HCC cell lines (SMMC-7721, Hep3B, HepG2 and Huh 7).The expression of Ki-67, a proliferation marker, was also reduced in SOX7-overexpression tumors.

View Article: PubMed Central - PubMed

Affiliation: Department of Basic Medical Sciences of Medical College, Xiamen University, Xiamen, Fujian, China.

ABSTRACT
SOX7 is a transcription factor mediating various developmental processes. However, its role in hepatocellular carcinoma (HCC) remains unclear. Here, we assessed the role of SOX7 in hepatocarcinogenesis. We found HCC samples exhibited lower levels of SOX7 mRNA and protein expression than non-tumor samples, and the expression of SOX7 was negatively correlated with tumor size. SOX7 expression was also reduced in four HCC cell lines (SMMC-7721, Hep3B, HepG2 and Huh 7). Overexpression of SOX7 could inhibit HCC cell growth, with G1to S phase arrest. In SOX7-overexpression cells, cyclin D1 and c-myc, two cell cycle promoters, were down-regulated. Moreover, ectopic expression of cyclin D1 or c-myc could override G1 to S pahse arrest induced by SOX7. Furthermore, overexpression of SOX7 suppressed tumor formation with down-regulation of cyclin D1 and c-myc in vivo. The expression of Ki-67, a proliferation marker, was also reduced in SOX7-overexpression tumors. Taken together, our study suggests that SOX7 plays an important inhibitory role in hepatocarcinogenesis, and might be a novel target for HCC therapy.

Show MeSH
Related in: MedlinePlus