RASSF10 suppresses hepatocellular carcinoma growth by activating P53 signaling and methylation of RASSF10 is a docetaxel resistant marker
Yongshuai Jin1,2, Baoping Cao1,3, Meiying Zhang1,3, Qimin Zhan4, James G. Herman5, Miao Yu2, Mingzhou Guo1
1 Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, Beijing, China.
2 Department of Interventional Radiology, Chinese PLA General Hospital, Beijing, China
3 Medical College of NanKai University, Tianjin, China
4 State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
5 The Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
Correspondence:
Mingzhou Guo, email:
Correspondence:
Miao Yu, email:
Keywords: RASSF10, DNA methylation, P53 signaling, hepatocellular carcinoma, epigenetics
Received: April 9, 2015 Accepted: May 28, 2015 Published: June 8, 2015
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.
