IRF-2 inhibits cancer proliferation by promoting AMER-1 transcription in human gastric cancer

J Transl Med. 2022 Feb 3;20(1):68. doi: 10.1186/s12967-022-03275-0.

Abstract

Background: Interferon regulatory factor 2 (IRF-2) acts as an anti-oncogene in gastric cancer (GC); however, the underlying mechanism remains unknown.

Methods: This study determined the expression of IRF-2 in GC tissues and adjacent non-tumor tissues using immunohistochemistry (IHC) and explored the predictive value of IRF-2 for the prognoses of GC patients. Cell function and xenograft tumor growth experiments in nude mice were performed to test tumor proliferation ability, both in vitro and in vivo. Chromatin immunoprecipitation sequencing (ChIP-Seq) assay was used to verify the direct target of IRF-2.

Results: We found that IRF-2 expression was downregulated in GC tissues and was negatively correlated with the prognoses of GC patients. IRF-2 negatively affected GC cell proliferation both in vitro and in vivo. ChIP-Seq assay showed that IRF-2 could directly activate AMER-1 transcription and regulate the Wnt/β-catenin signaling pathway, which was validated using IHC, in both tissue microarray and xenografted tumor tissues, western blot analysis, and cell function experiments.

Conclusions: Increased expression of IRF-2 can inhibit tumor growth and affect the prognoses of patients by directly regulating AMER-1 transcription in GC and inhibiting the Wnt/β-catenin signaling pathway.

Keywords: AMER-1; Gastric cancer; IRF-2; Prognosis; wnt/β-catenin signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Interferon Regulatory Factor-2 / genetics
  • Interferon Regulatory Factor-2 / metabolism
  • Mice
  • Mice, Nude
  • Stomach Neoplasms* / pathology
  • Tumor Suppressor Proteins
  • Wnt Signaling Pathway
  • beta Catenin / metabolism

Substances

  • AMER1 protein, human
  • Adaptor Proteins, Signal Transducing
  • IRF2 protein, human
  • Interferon Regulatory Factor-2
  • Tumor Suppressor Proteins
  • beta Catenin