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RASSF10 suppresses hepatocellular carcinoma growth by activating P53 signaling and methylation of RASSF10 is a docetaxel resistant marker.

Jin Y, Cao B, Zhang M, Zhan Q, Herman JG, Yu M, Guo M - Genes Cancer (2015)

Bottom Line: Our previous study found that RASSF10 suppresses colorectal cancer growth by activating P53 signaling.In conclusion, we demonstrated that RASSF10 is frequently methylated in human HCC and its methylation is a potential docetaxel resistant marker.Our data also indicate that RASSF10 suppresses human HCC growth by activating P53 signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China ; Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, China.

ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common malignances and the second leading cause of cancer related death worldwide. RASSF10 is located on chromosome 11p15.2, a region that shows frequent loss of heterozygosity (LOH) in several cancer types. Our previous study found that RASSF10 suppresses colorectal cancer growth by activating P53 signaling. To explore the epigenetic changes and the mechanism of RASSF10 in human HCC, 69 cases of primary HCC, twenty cases of normal liver tissue samples and 17 HCC cell lines were involved in this study. We found that RASSF10 was methylated in 82.6% (57/69) of human primary HCC and methylation of RASSF10 was significantly associated with tumor size (P < 0.05) and TNM stage (P < 0.05). The expression of RASSF10 was regulated by promoter region methylation. Restoration of RASSF10 expression suppressed cell proliferation, induced apoptosis and G2/M phase arrest, as well as sensitized cells to docetaxel and activated P53 signaling in HepG2 and QGY7703 cells. In conclusion, we demonstrated that RASSF10 is frequently methylated in human HCC and its methylation is a potential docetaxel resistant marker. Our data also indicate that RASSF10 suppresses human HCC growth by activating P53 signaling.

No MeSH data available.


Related in: MedlinePlus

The role of RASSF10 in apoptosis and P53 signaling in human HCC cells(A) Flow cytometry results show the role of RASSF10 in apoptosis in HepG2 and QGY7703 cells. * P < 0.05. (B) Western blots show the effects of RASSF10 on survivin, capase-3, cleaved capase-3, P21 and bcl-2 expression in HepG2 and QGY7703 cells. β-actin: internal control. (C) Western blots demonstrate the role of RASSF10 in MDM2, P53, P21, bcl-2 and BAX expression in HepG2 and QGY7703 cells. β-actin: internal control. (D) The expression of MDM2, P53, P21, bcl-2 and BAX was detected by western blot after knocking down RASSF10 in DKO cells. β-actin: internal control.
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Figure 6: The role of RASSF10 in apoptosis and P53 signaling in human HCC cells(A) Flow cytometry results show the role of RASSF10 in apoptosis in HepG2 and QGY7703 cells. * P < 0.05. (B) Western blots show the effects of RASSF10 on survivin, capase-3, cleaved capase-3, P21 and bcl-2 expression in HepG2 and QGY7703 cells. β-actin: internal control. (C) Western blots demonstrate the role of RASSF10 in MDM2, P53, P21, bcl-2 and BAX expression in HepG2 and QGY7703 cells. β-actin: internal control. (D) The expression of MDM2, P53, P21, bcl-2 and BAX was detected by western blot after knocking down RASSF10 in DKO cells. β-actin: internal control.

Mentions: To explore the role of RASSF10 in apoptosis, flow cytometry was performed. The percentage of apoptotic cells was 3.26 ± 0.66% vs 10.31 ± 2.38% in HepG2 cells (P<0.05) and 5.37 ± 0.16% vs 14.26 ± 3.00% in QGY7703 cells (P<0.05) before and after re-expression of RASSF10. These results suggest that RASSF10 induced cell apoptosis in HCC cells (Figure 6A). To further explore the mechanisms of RASSF10 in HCC cell apoptosis, survivin, capase-3, cleaved capase-3, P21 and bcl-2 levels were examined by western blot before and after re-expression of RASSF10. The expression levels of cleaved capase-3 and P21 were increased, while surviving, capase-3 and bcl-2 were reduced after re-expression of RASSF10 in HepG2 and QGY7703 cells (Figure 6B).


RASSF10 suppresses hepatocellular carcinoma growth by activating P53 signaling and methylation of RASSF10 is a docetaxel resistant marker.

Jin Y, Cao B, Zhang M, Zhan Q, Herman JG, Yu M, Guo M - Genes Cancer (2015)

The role of RASSF10 in apoptosis and P53 signaling in human HCC cells(A) Flow cytometry results show the role of RASSF10 in apoptosis in HepG2 and QGY7703 cells. * P < 0.05. (B) Western blots show the effects of RASSF10 on survivin, capase-3, cleaved capase-3, P21 and bcl-2 expression in HepG2 and QGY7703 cells. β-actin: internal control. (C) Western blots demonstrate the role of RASSF10 in MDM2, P53, P21, bcl-2 and BAX expression in HepG2 and QGY7703 cells. β-actin: internal control. (D) The expression of MDM2, P53, P21, bcl-2 and BAX was detected by western blot after knocking down RASSF10 in DKO cells. β-actin: internal control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 6: The role of RASSF10 in apoptosis and P53 signaling in human HCC cells(A) Flow cytometry results show the role of RASSF10 in apoptosis in HepG2 and QGY7703 cells. * P < 0.05. (B) Western blots show the effects of RASSF10 on survivin, capase-3, cleaved capase-3, P21 and bcl-2 expression in HepG2 and QGY7703 cells. β-actin: internal control. (C) Western blots demonstrate the role of RASSF10 in MDM2, P53, P21, bcl-2 and BAX expression in HepG2 and QGY7703 cells. β-actin: internal control. (D) The expression of MDM2, P53, P21, bcl-2 and BAX was detected by western blot after knocking down RASSF10 in DKO cells. β-actin: internal control.
Mentions: To explore the role of RASSF10 in apoptosis, flow cytometry was performed. The percentage of apoptotic cells was 3.26 ± 0.66% vs 10.31 ± 2.38% in HepG2 cells (P<0.05) and 5.37 ± 0.16% vs 14.26 ± 3.00% in QGY7703 cells (P<0.05) before and after re-expression of RASSF10. These results suggest that RASSF10 induced cell apoptosis in HCC cells (Figure 6A). To further explore the mechanisms of RASSF10 in HCC cell apoptosis, survivin, capase-3, cleaved capase-3, P21 and bcl-2 levels were examined by western blot before and after re-expression of RASSF10. The expression levels of cleaved capase-3 and P21 were increased, while surviving, capase-3 and bcl-2 were reduced after re-expression of RASSF10 in HepG2 and QGY7703 cells (Figure 6B).

Bottom Line: Our previous study found that RASSF10 suppresses colorectal cancer growth by activating P53 signaling.In conclusion, we demonstrated that RASSF10 is frequently methylated in human HCC and its methylation is a potential docetaxel resistant marker.Our data also indicate that RASSF10 suppresses human HCC growth by activating P53 signaling.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China ; Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, China.

ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most common malignances and the second leading cause of cancer related death worldwide. RASSF10 is located on chromosome 11p15.2, a region that shows frequent loss of heterozygosity (LOH) in several cancer types. Our previous study found that RASSF10 suppresses colorectal cancer growth by activating P53 signaling. To explore the epigenetic changes and the mechanism of RASSF10 in human HCC, 69 cases of primary HCC, twenty cases of normal liver tissue samples and 17 HCC cell lines were involved in this study. We found that RASSF10 was methylated in 82.6% (57/69) of human primary HCC and methylation of RASSF10 was significantly associated with tumor size (P < 0.05) and TNM stage (P < 0.05). The expression of RASSF10 was regulated by promoter region methylation. Restoration of RASSF10 expression suppressed cell proliferation, induced apoptosis and G2/M phase arrest, as well as sensitized cells to docetaxel and activated P53 signaling in HepG2 and QGY7703 cells. In conclusion, we demonstrated that RASSF10 is frequently methylated in human HCC and its methylation is a potential docetaxel resistant marker. Our data also indicate that RASSF10 suppresses human HCC growth by activating P53 signaling.

No MeSH data available.


Related in: MedlinePlus