EIF3i promotes colon oncogenesis by regulating COX-2 protein synthesis and β-catenin activation

J. Qi, Zizheng Dong, J. Liu, Jian-Ting Zhang

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Translational control of gene expression has recently been recognized as an important mechanism controlling cell proliferation and oncogenesis, and it mainly occurs in the initiation step of protein synthesis that involves multiple eukaryotic initiation factors (eIFs). Many eIFs have been found to have aberrant expression in human tumors and the aberrant expression may contribute to oncogenesis. However, how these previously considered house-keeping proteins are potentially oncogenic remains elusive. In this study, we investigated the expression of eIF3i in human colon cancers, tested its contribution to colon oncogenesis and determined the mechanism of eIF3i action in colon oncogenesis. We found that eIF3i expression was upregulated in both human colon adenocarcinoma and adenoma polyps as well as in model inducible colon tumorigenic cell lines. Overexpression of ectopic eIF3i in intestinal epithelial cells causes oncogenesis by directly upregulating the synthesis of cyclooxygenase-2 (COX-2) protein and activates the β-catenin/T-cell factor 4 signaling pathway that mediates the oncogenic function of eIF3i. Together, we conclude that eIF3i is a proto-oncogene that drives colon oncogenesis by translationally upregulating COX-2 and activating the β-catenin signaling pathway. These findings imply that proto-oncogenic eIFs likely exert their tumorigenic function by regulating/altering the synthesis level of downstream tumor suppressor or oncogenes.

Original languageEnglish
Pages (from-to)4156-4163
Number of pages8
JournalOncogene
Volume33
Issue number32
DOIs
StatePublished - Aug 7 2014

Fingerprint

Catenins
Cyclooxygenase 2
Colon
Carcinogenesis
Eukaryotic Initiation Factors
Transcription Factor 7-Like 2 Protein
Proto-Oncogenes
Polyps
Oncogenes
Adenoma
Colonic Neoplasms
Neoplasms
Proteins
Adenocarcinoma
Epithelial Cells
Cell Proliferation
Gene Expression
Cell Line

Keywords

  • b-catenin
  • colon cancer
  • COX-2
  • eIF3i
  • RNA-binding
  • translational control

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

EIF3i promotes colon oncogenesis by regulating COX-2 protein synthesis and β-catenin activation. / Qi, J.; Dong, Zizheng; Liu, J.; Zhang, Jian-Ting.

In: Oncogene, Vol. 33, No. 32, 07.08.2014, p. 4156-4163.

Research output: Contribution to journalArticle

Qi, J. ; Dong, Zizheng ; Liu, J. ; Zhang, Jian-Ting. / EIF3i promotes colon oncogenesis by regulating COX-2 protein synthesis and β-catenin activation. In: Oncogene. 2014 ; Vol. 33, No. 32. pp. 4156-4163.
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