BORIS up-regulates OCT4 via histone methylation to promote cancer stem cell-like properties in human liver cancer cells. (10th September 2017)

• Record Type: Journal Article
• Authors: Liu, Qiuying; Chen, Kefei; Liu, Zhongjian; Huang, Yuan; Zhao, Rongce; Wei, Ling; Yu, Xiaoqin; He, Jingyang; Liu, Jun; Qi, Jianguo; Qin, Yang; Li, Bo
• Is Part Of: Cancer letters. Volume 403(2017)
• Page Start: 165
• Page End: 174
• Publication Date: 2017-09-10
• Subjects: BORIS -- Liver cancer -- Cancer stem cell -- Epigenetic regulation -- OCT4; BORIS Brother of the Regulator of Imprinted Sites -- CTCFL CCCTC-binding factor-like -- CSC cancer stem cell -- HCC hepatocellular carcinoma -- DOX doxorubicin -- EMT epithelial-mesenchymal transition -- ChIP chromatin immunoprecipitation -- BSP bisulfite genomic sequencing polymerase chain reaction -- MSP methylation-specific polymerase chain reaction; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2017.06.017
• Languages: English
• ISSNs: 0304-3835

Abstract

Abstract: Accumulating evidence has revealed the importance of cancer stem cells (CSCs) in chemoresistance and recurrence. BORIS, a testes-specific CTCF paralog, has been shown to be associated with stemness traits of embryonic cancer cells and epithelial CSCs. We previously reported that BORIS is correlated with the expression of the CSC marker CD90 in hepatocellular carcinoma (HCC). These results encourage us to wonder whether BORIS exerts functions on CSC-like traits of human liver cancer cells. Here, we report that BORIS was enriched in HCC tissues. Exogenous overexpression of BORIS promoted CSC-like properties, including self-renewal, chemoresistance, migration and invasion in Huh7 and HCCLM3 cells. Conversely, BORIS knockdown suppressed CSC-like properties in SMMC-7721 and HepG2 cells and inhibited tumorigenicity in SMMC-7721 cells. Moreover, BORIS alteration did not affect the DNA methylation status of the minimal promoter and exon 1 region of OCT 4. However, BORIS overexpression enhanced the amount of BORIS bound on the OCT 4 promoter and increased H3K4me2, while reducing H3K27me3; BORIS depletion decreased BORIS and H3K4me2 on the OCT 4 promoter, while increasing H3K27me3. These results revealed that BORIS is associated with the CSC-like traits of human liver cancer cells through the epigenetic regulation of OCT4. Highlights: BORIS was enriched in HCC tissues. BORIS facilitates the CSC-like properties of human liver cancer cells. BORIS positively regulates expressions of CD90, OCT4, SOX2 and c-Myc. BORIS regulates OCT4 gene expression through histone methylation modification.