SEI1 induces genomic instability by inhibiting DNA damage response in ovarian cancer

Cancer Lett. 2017 Jan 28;385:271-279. doi: 10.1016/j.canlet.2016.09.032. Epub 2016 Oct 3.


Previous studies have shown that the oncogene SEI1 is highly expressed in ovarian carcinomas, and promoting genomic instability. However, the molecular mechanism of SEI1 in promoting genomic instability remains unclear. We observed SEI1 overexpression in 30 of 46 cases of ovarian cancer compared to non-tumor tissues and the overexpression of SEI1 was positively associated with the tumor FIGO stage. Our functional studies revealed that overexpression of SEI1 could induce genomic instability and increased DNA strand breaks. In contrast, SEI1 co-localized with γH2AX and phosphorylated ATM and DNAPKcs in the nucleus. Furthermore, we found that overexpression of SEI1 induced translocation of the SEI1 protein from the cytoplasm to the nucleus; ATM and DNAPKcs were associated with the cytoplasm-to-nucleus translocation of SEI1. To further prove the correlation between the DNA damage response (DDR) and SEI1, we knocked down SEI1 expression in SEI1-transfected ovarian cancer cell lines. The expression of DDR proteins was significantly downregulated, and the number of micronuclei was significantly decreased. Together, these results define a new mechanism of SEI1 in the regulation of genomic stability and in the malignant progression of ovarian cancer.

Keywords: DDR; Genomic instability; Ovarian cancer; SEI1; SERTAD1.

MeSH terms

  • Active Transport, Cell Nucleus
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Calcium-Binding Proteins / metabolism
  • Cell Line, Tumor
  • DNA Damage*
  • DNA Repair*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genomic Instability*
  • Histones / metabolism
  • Humans
  • Middle Aged
  • Neoplasm Staging
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Phosphorylation
  • RNA Interference
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors
  • Transfection
  • Up-Regulation


  • Biomarkers, Tumor
  • CIB1 protein, human
  • Calcium-Binding Proteins
  • H2AX protein, human
  • Histones
  • Nuclear Proteins
  • SERTAD1 protein, human
  • Trans-Activators
  • Transcription Factors
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins