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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 effect of RASSF10 on cell cycle and the sensitivity of HCC cells to docetaxel(A) Cell phase distribution in RASSF10 unexpressed and re-expressed HepG2 and QGY7703 cells. The ratios are presented by bar diagram. Each experiment was repeated three times. * P < 0.05. (B) The expression of RASSF10, cyclin B1 and cdc-2 was detected by western blot in RASSF10 unexpressed and re-expressed HepG2 and QGY7703 cells. β-actin: internal control. (C) The cell viability analysis shows the sensitivity of RASSF10 re-expressed or unexpressed HepG2 and QGY7703 cells to docetaxel. *P <0.05.
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Figure 5: The effect of RASSF10 on cell cycle and the sensitivity of HCC cells to docetaxel(A) Cell phase distribution in RASSF10 unexpressed and re-expressed HepG2 and QGY7703 cells. The ratios are presented by bar diagram. Each experiment was repeated three times. * P < 0.05. (B) The expression of RASSF10, cyclin B1 and cdc-2 was detected by western blot in RASSF10 unexpressed and re-expressed HepG2 and QGY7703 cells. β-actin: internal control. (C) The cell viability analysis shows the sensitivity of RASSF10 re-expressed or unexpressed HepG2 and QGY7703 cells to docetaxel. *P <0.05.

Mentions: The role of RASSF10 in the cell cycle was analyzed by flow cytometry. As shown in Figure 5A, the distribution of cell phase in RASSF10 unexpressed and re-expressed HepG2 cells was 64.22 ± 3.0% vs. 54.57 ± 0.7% in G0/G1 phase, 22.88 ± 0.3% vs. 24.96 ± 1.1% in S phase and 12.9 ± 2.7% vs. 20.48 ± 1.7% in G2/M phase. In QGY7703 cells, the cell phase distribution was 54.65 ± 0.4% vs. 42.26 ± 1.8% in G0/G1 phase, 31.54 ± 1.3% vs. 35.28 ± 2.1% in S phase and 13.81 ± 1.0% vs. 22.45 ± 0.5% in G2/M phase before and after restoration of RASSF10 expression. The G0/G1 phase was significantly reduced and the G2/M phase was significantly increased before and after re-expression of RASSF10 in HCC cells (all P<0.05). The G1/S checkpoint was not obviously affected by RASSF10, as S phase was not changed significantly (P>0.05). The effect of RASSF10 on the arrest of the G2/M checkpoint was further validated by detecting G2/M phase related proteins in HCC cells. The expression levels of cyclin B1 and cdc-2, important G2/M checkpoint regulators, were dramatically reduced after re-expression of RASSF10 in HepG2 and QGY7703 cells (Figure 5B).


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 effect of RASSF10 on cell cycle and the sensitivity of HCC cells to docetaxel(A) Cell phase distribution in RASSF10 unexpressed and re-expressed HepG2 and QGY7703 cells. The ratios are presented by bar diagram. Each experiment was repeated three times. * P < 0.05. (B) The expression of RASSF10, cyclin B1 and cdc-2 was detected by western blot in RASSF10 unexpressed and re-expressed HepG2 and QGY7703 cells. β-actin: internal control. (C) The cell viability analysis shows the sensitivity of RASSF10 re-expressed or unexpressed HepG2 and QGY7703 cells to docetaxel. *P <0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482244&req=5

Figure 5: The effect of RASSF10 on cell cycle and the sensitivity of HCC cells to docetaxel(A) Cell phase distribution in RASSF10 unexpressed and re-expressed HepG2 and QGY7703 cells. The ratios are presented by bar diagram. Each experiment was repeated three times. * P < 0.05. (B) The expression of RASSF10, cyclin B1 and cdc-2 was detected by western blot in RASSF10 unexpressed and re-expressed HepG2 and QGY7703 cells. β-actin: internal control. (C) The cell viability analysis shows the sensitivity of RASSF10 re-expressed or unexpressed HepG2 and QGY7703 cells to docetaxel. *P <0.05.
Mentions: The role of RASSF10 in the cell cycle was analyzed by flow cytometry. As shown in Figure 5A, the distribution of cell phase in RASSF10 unexpressed and re-expressed HepG2 cells was 64.22 ± 3.0% vs. 54.57 ± 0.7% in G0/G1 phase, 22.88 ± 0.3% vs. 24.96 ± 1.1% in S phase and 12.9 ± 2.7% vs. 20.48 ± 1.7% in G2/M phase. In QGY7703 cells, the cell phase distribution was 54.65 ± 0.4% vs. 42.26 ± 1.8% in G0/G1 phase, 31.54 ± 1.3% vs. 35.28 ± 2.1% in S phase and 13.81 ± 1.0% vs. 22.45 ± 0.5% in G2/M phase before and after restoration of RASSF10 expression. The G0/G1 phase was significantly reduced and the G2/M phase was significantly increased before and after re-expression of RASSF10 in HCC cells (all P<0.05). The G1/S checkpoint was not obviously affected by RASSF10, as S phase was not changed significantly (P>0.05). The effect of RASSF10 on the arrest of the G2/M checkpoint was further validated by detecting G2/M phase related proteins in HCC cells. The expression levels of cyclin B1 and cdc-2, important G2/M checkpoint regulators, were dramatically reduced after re-expression of RASSF10 in HepG2 and QGY7703 cells (Figure 5B).

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