CNBP controls tumor cell biology by regulating tumor-promoting gene expression

Mol Carcinog. 2019 Aug;58(8):1492-1501. doi: 10.1002/mc.23030. Epub 2019 May 13.

Abstract

Cellular nucleic acid-binding protein (CNBP) is associated with cell proliferation, and its expression is elevated in human tumors, but the molecular mechanisms of CNBP in tumor cell biology have not been fully elucidated. In this study, we report that CNBP is a transcription factor essential for regulating matrix metalloproteinases mmp-2, mmp-14, and transcription factor e2f2 gene expression by binding to their promoter regions via a sequence-specific manner. Importantly, epidermal growth factor stimulation is required to induce CNBP phosphorylation and nuclear transport, thereby promoting the expression of mmp-2, mmp-14, and e2f2 genes. As a consequence, loss of cnbp attenuates the ability of tumor cell growth, invasion, and migration. Conversely, overexpression of cnbp is associated with tumor cell biology. Collectively, our findings reveal CNBP as a key transcriptional regulator of tumor-promoting target genes to control tumor cell biology.

Keywords: cellular nucleic acid-binding protein; extracellular matrix; matrix metalloproteinase; transcription factor; tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Cell Line
  • Cell Proliferation
  • E2F2 Transcription Factor / biosynthesis*
  • E2F2 Transcription Factor / genetics
  • HEK293 Cells
  • Humans
  • Matrix Metalloproteinase 14 / biosynthesis*
  • Matrix Metalloproteinase 14 / genetics
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 2 / genetics
  • Mice
  • Neoplasms / genetics
  • Neoplasms / pathology*
  • Phosphorylation
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • RNA, Messenger / biosynthesis
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Transcription, Genetic / genetics
  • Up-Regulation / genetics

Substances

  • Cnbp1 protein, mouse
  • E2F2 Transcription Factor
  • E2f2 protein, mouse
  • Mmp14 protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 14