NF-YA promotes the cell proliferation and tumorigenic properties by transcriptional activation of SOX2 in cervical cancer

J Cell Mol Med. 2020 Nov;24(21):12464-12475. doi: 10.1111/jcmm.15777. Epub 2020 Sep 20.

Abstract

NF-YA is considered as a crucial regulator for the maintenance of cancer stem cell (CSC) and involved in various types of malignant tumours. However, the exact function and molecular mechanisms of NF-YA in the progression of cervical cancer remains poorly understood. Here, the expression of NF-YA detected by immunohistochemistry was gradually increased from normal cervical tissues, to the high-grade squamous intraepithelial lesions, and then to cervical cancer tissues. NF-YA promoted the cell proliferation and tumorigenic properties of cervical cancer cells as well as tumorsphere formation and chemoresistance in vitro. The luciferase reporter assay combined with mutagenesis analyses and Western blotting showed that NF-YA trans-activated the expression of SOX2 in cervical cancer. Furthermore, quantitative chromatin immunoprecipitation (qChIP) and electrophoretic mobility shift assay (EMSA) confirmed that NF-YA protein directly bound to the CCAAT box region located upstream of the SOX2 promoter. Together, our data demonstrated that NF-YA was highly expressed in cervical cancer and promoted the cell proliferation, tumorigenicity and CSC characteristic by trans-activating the expression of SOX2.

Keywords: NF-YA; SOX2; cancer stem cell; cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CCAAT-Binding Factor / metabolism*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Separation
  • Cell Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplastic Stem Cells / metabolism
  • SOXB1 Transcription Factors / metabolism*
  • Transcriptional Activation
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Neoplasms / metabolism*

Substances

  • CCAAT-Binding Factor
  • NFYA protein, human
  • Nfya protein, mouse
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Sox2 protein, mouse