BORIS up-regulates OCT4 via histone methylation to promote cancer stem cell-like properties in human liver cancer cells

Cancer Lett. 2017 Sep 10:403:165-174. doi: 10.1016/j.canlet.2017.06.017. Epub 2017 Jun 20.

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 OCT4. However, BORIS overexpression enhanced the amount of BORIS bound on the OCT4 promoter and increased H3K4me2, while reducing H3K27me3; BORIS depletion decreased BORIS and H3K4me2 on the OCT4 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.

Keywords: BORIS; Cancer stem cell; Epigenetic regulation; Liver cancer; OCT4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Binding Sites
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Movement
  • Cell Proliferation
  • Cell Self Renewal
  • DNA Methylation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm
  • Epigenesis, Genetic
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Histones / metabolism*
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Methylation
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism*
  • Phenotype
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Signal Transduction
  • Thy-1 Antigens / genetics
  • Thy-1 Antigens / metabolism
  • Time Factors
  • Transfection
  • Tumor Burden
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Antibiotics, Antineoplastic
  • CTCFL protein, human
  • DNA-Binding Proteins
  • Histones
  • MYC protein, human
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proto-Oncogene Proteins c-myc
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Thy-1 Antigens
  • Doxorubicin