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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

Representative results of RASSF10 methylation and expression in primary HCC(A) Representative MSP results of RASSF10 in normal human liver (N1-N5) and primary HCC (HCC1-HCC8) tissue samples. N: normal liver tissue samples. HCC: hepatocellular carcinoma tissue samples. (B) Representative IHC results of RASSF10 expression in HCC and adjacent tissue samples (upper boxes, 200×; lower boxes 400×). (C) RASSF10 expression scores are shown as box plots, horizontal lines represent the median score; the bottom and top of the boxes represent the 25th and 75th percentiles, respectively; vertical bars represent the range of data. Expression of RASSF10 was different between adjacent tissue samples and HCC tissue samples in 31 cases of primary HCC tissue samples. **P<0.01. (D) The expression of RASSF10 and DNA methylation status is shown as a bar diagram. Reduced expression of RASSF10 was significantly associated with promoter region hypermethylation. *P<0.05.
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Figure 3: Representative results of RASSF10 methylation and expression in primary HCC(A) Representative MSP results of RASSF10 in normal human liver (N1-N5) and primary HCC (HCC1-HCC8) tissue samples. N: normal liver tissue samples. HCC: hepatocellular carcinoma tissue samples. (B) Representative IHC results of RASSF10 expression in HCC and adjacent tissue samples (upper boxes, 200×; lower boxes 400×). (C) RASSF10 expression scores are shown as box plots, horizontal lines represent the median score; the bottom and top of the boxes represent the 25th and 75th percentiles, respectively; vertical bars represent the range of data. Expression of RASSF10 was different between adjacent tissue samples and HCC tissue samples in 31 cases of primary HCC tissue samples. **P<0.01. (D) The expression of RASSF10 and DNA methylation status is shown as a bar diagram. Reduced expression of RASSF10 was significantly associated with promoter region hypermethylation. *P<0.05.

Mentions: To determine the methylation status of RASSF10 in human primary HCC, 69 cases of primary HCC and 20 cases of normal liver tissue samples were examined by MSP. RASSF10 was methylated in 82.6% (57/69) of primary HCC samples, but no methylation was detected in normal liver tissue samples (Figure 3A). As shown in Table 1, methylation of RASSF10 was significantly associated with tumor size (P < 0.05) and tumor stage (P < 0.05), but no association was found between RASSF10 methylation and age, gender, HBV infection, cirrhosis, lymph node metastasis and cell differentiation. The expression of RASSF10 was evaluated by immunohistochemistry (IHC) in 31 cases of available matched primary HCC and adjacent tissue samples. Staining of RASSF10 was mainly localized in the cytoplasm and its expression was significantly reduced in primary HCC compared to adjacent tissue samples (p<0.05, Figure 3B and C). In 31 cases of available primary hepatic cancer samples, loss or reduced expression of RASSF10 was found in 24 cases. Of these 24 case samples, 22 cases were methylated and 2 cases were unmethylated. Loss or reduced expression of RASSF10 was significantly associated with promoter region hypermethylation (p<0.05, Figure 3D). These results indicate that RASSF10 expression is regulated by promoter region methylation in primary HCC.


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)

Representative results of RASSF10 methylation and expression in primary HCC(A) Representative MSP results of RASSF10 in normal human liver (N1-N5) and primary HCC (HCC1-HCC8) tissue samples. N: normal liver tissue samples. HCC: hepatocellular carcinoma tissue samples. (B) Representative IHC results of RASSF10 expression in HCC and adjacent tissue samples (upper boxes, 200×; lower boxes 400×). (C) RASSF10 expression scores are shown as box plots, horizontal lines represent the median score; the bottom and top of the boxes represent the 25th and 75th percentiles, respectively; vertical bars represent the range of data. Expression of RASSF10 was different between adjacent tissue samples and HCC tissue samples in 31 cases of primary HCC tissue samples. **P<0.01. (D) The expression of RASSF10 and DNA methylation status is shown as a bar diagram. Reduced expression of RASSF10 was significantly associated with promoter region hypermethylation. *P<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Representative results of RASSF10 methylation and expression in primary HCC(A) Representative MSP results of RASSF10 in normal human liver (N1-N5) and primary HCC (HCC1-HCC8) tissue samples. N: normal liver tissue samples. HCC: hepatocellular carcinoma tissue samples. (B) Representative IHC results of RASSF10 expression in HCC and adjacent tissue samples (upper boxes, 200×; lower boxes 400×). (C) RASSF10 expression scores are shown as box plots, horizontal lines represent the median score; the bottom and top of the boxes represent the 25th and 75th percentiles, respectively; vertical bars represent the range of data. Expression of RASSF10 was different between adjacent tissue samples and HCC tissue samples in 31 cases of primary HCC tissue samples. **P<0.01. (D) The expression of RASSF10 and DNA methylation status is shown as a bar diagram. Reduced expression of RASSF10 was significantly associated with promoter region hypermethylation. *P<0.05.
Mentions: To determine the methylation status of RASSF10 in human primary HCC, 69 cases of primary HCC and 20 cases of normal liver tissue samples were examined by MSP. RASSF10 was methylated in 82.6% (57/69) of primary HCC samples, but no methylation was detected in normal liver tissue samples (Figure 3A). As shown in Table 1, methylation of RASSF10 was significantly associated with tumor size (P < 0.05) and tumor stage (P < 0.05), but no association was found between RASSF10 methylation and age, gender, HBV infection, cirrhosis, lymph node metastasis and cell differentiation. The expression of RASSF10 was evaluated by immunohistochemistry (IHC) in 31 cases of available matched primary HCC and adjacent tissue samples. Staining of RASSF10 was mainly localized in the cytoplasm and its expression was significantly reduced in primary HCC compared to adjacent tissue samples (p<0.05, Figure 3B and C). In 31 cases of available primary hepatic cancer samples, loss or reduced expression of RASSF10 was found in 24 cases. Of these 24 case samples, 22 cases were methylated and 2 cases were unmethylated. Loss or reduced expression of RASSF10 was significantly associated with promoter region hypermethylation (p<0.05, Figure 3D). These results indicate that RASSF10 expression is regulated by promoter region methylation in primary HCC.

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