J Cancer 2017; 8(16):3318-3330. doi:10.7150/jca.20482
Histone Methyltransferase SETDB1 Promotes the Progression of Colorectal Cancer by Inhibiting the Expression of TP53
1. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China;
2. HuiQiao Medical Center, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
* These authors contributed equally to this work.
Chen K, Zhang F, Ding J, Liang Y, Zhan Z, Zhan Y, Chen Lh, Ding Y. Histone Methyltransferase SETDB1 Promotes the Progression of Colorectal Cancer by Inhibiting the Expression of TP53. J Cancer 2017; 8(16):3318-3330. doi:10.7150/jca.20482. Available from http://www.jcancer.org/v08p3318.htm
SETDB1 is a novel histone methyltransferase associated with the functional tri-methylation of histone H3K9. Although aberrant high expression of SETDB1 was experimentally obversed in a variety of solid tumors, its underlying mechanisms in human carcinogenesis are not well known. In this study, we investigated the expression of SETDB1 in a large cohort of colorectal cancer (CRC) samples and cell lines for the first time. Our findings showed that SETDB1 was highly expressed in majority CRC tissues and cell lines; moreover, up-regulation of SETDB1 was negatively correlated with the survival rate of CRC patients. Functionally, over-expression of SETDB1 significantly promoted the proliferation and migration of CRC cells in vitro and in vivo, while knocking down SETDB1 suppressed their growth. Mechanistically, we showed that over-expression of SETDB1 significantly inhibited the apoptosis induced by 5-Fluorouracil in CRC cells, which was closely related to the inhibition of TP53 and BAX expression. Furthermore, we confirmed that SETDB1 could be recruited to the promoter region of TP53, which might contribute its inhibition of apoptosis. For conclusion, our study indicated that SETDB1 is essential for colorectal carcinogenesis, and may be a newly target for treatment and prognostic evaluation in CRC.
Keywords: Histone Methyltransferase, SETDB1, Colorectal Cancer, TP53, Apoptosis.