The expression of the embryonic gene Cripto-1 is regulated by OCT4 in human embryonal carcinoma NCCIT cells

FEBS Lett. 2018 Jan;592(1):24-35. doi: 10.1002/1873-3468.12935. Epub 2017 Dec 22.

Abstract

Cripto-1 and OCT4, expressed in stem cells and cancers, play important roles in tumorigenesis. Here, we demonstrate that Cripto-1 expression is regulated by OCT4 in human embryonic carcinoma NCCIT cells. The endogenous expression of Cripto-1 and OCT4 is significantly reduced during differentiation. Cripto-1 expression is increased by OCT4 overexpression, but decreased by shRNA-mediated OCT4 knockdown. OCT4 overexpression significantly activates Cripto-1 transcriptional activity. A 5'-upstream minimal promoter sequence in the gene-encoding Cripto-1 is significantly activated by OCT4 overexpression. Mutation of the putative OCT4-binding site abolishes OCT4-mediated activation of the Cripto-1 promoter. The OCT4 transactivation domains mediate transcriptional activity of the Cripto-1 minimal promoter through direct interaction. Taken together, OCT4 plays an important role as a transcriptional activator of Cripto-1 expression in NCCIT cells.

Keywords: Cripto-1; NCCIT cells; OCT4; minimal promoter; transcriptional activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / genetics
  • Carcinoma, Embryonal / genetics*
  • Carcinoma, Embryonal / metabolism
  • Cell Differentiation
  • Cell Line, Tumor
  • GPI-Linked Proteins / genetics*
  • GPI-Linked Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mutation
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Octamer Transcription Factor-3 / antagonists & inhibitors
  • Octamer Transcription Factor-3 / genetics*
  • Octamer Transcription Factor-3 / metabolism
  • Promoter Regions, Genetic
  • RNA, Small Interfering / genetics
  • Transcriptional Activation

Substances

  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Small Interfering
  • TDGF1 protein, human