Ring finger protein 2 promotes colorectal cancer progression by suppressing early growth response 1

Aging (Albany NY). 2020 Dec 19;12(24):26199-26220. doi: 10.18632/aging.202396. Epub 2020 Dec 19.

Abstract

Ring finger protein 2 (RNF2) is an important component of polycomb repressive complex 1. RNF2 is upregulated in many kinds of tumors, and elevated RNF2 expression is associated with a poor prognosis in certain cancers. To assess the function of RNF2 in colorectal cancer, we examined RNF2 protein levels in 313 paired colorectal cancer tissues and adjacent normal tissues. We then analyzed the association of RNF2 expression with the patients' clinicopathologic features and prognoses. RNF2 expression was upregulated in colorectal cancer tissues and was associated with the tumor differentiation status, tumor stage and prognosis. In colorectal cancer cell lines, downregulation of RNF2 inhibited cell proliferation and induced apoptosis. Gene microarray analysis revealed that early growth response 1 (EGR1) was upregulated in RNF2-knockdown cells. Knocking down EGR1 partially reversed the inhibition of cell proliferation and the induction of apoptosis in RNF2-knockdown cells. RNF2 was enriched at the EGR1 promoter, where it mono-ubiquitinated histone H2A, thereby inhibiting EGR1 expression. These results indicate that RNF2 is oncogenic in colorectal cancer and may promote disease progression by inhibiting EGR1 expression. RNF2 is thus a potential prognostic marker and therapeutic target in colorectal cancer.

Keywords: EGR1; RNF2; apoptosis; cell proliferation; colorectal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Early Growth Response Protein 1 / genetics*
  • Early Growth Response Protein 1 / metabolism
  • Female
  • Gene Expression
  • Gene Knockdown Techniques
  • HCT116 Cells
  • Histone Code / genetics
  • Humans
  • Male
  • Middle Aged
  • Polycomb Repressive Complex 1 / genetics*
  • Polycomb Repressive Complex 1 / metabolism
  • Prognosis
  • Promoter Regions, Genetic
  • Ubiquitination
  • Up-Regulation

Substances

  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Polycomb Repressive Complex 1
  • RNF2 protein, human