Abstract
BackgroundInterferon regulatory factor 2 (IRF-2) acts as an anti-oncogene in gastric cancer (GC); however, the underlying mechanism remains unknown.MethodsThis 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.ResultsWe 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.ConclusionsIncreased 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.
Highlights
Interferon regulatory factor 2 (IRF-2) acts as an anti-oncogene in gastric cancer (GC); the underlying mechanism remains unknown
The interferon regulatory factor (IRF)‐2 expression was downregulated in GC tissue and related with prognosis The expression level of IRF-2 was examined in tissue microarrays (TMAs) containing 72 pairs of GC tissues and normal adjacent tissues by immu‐ nohistochemistry (IHC) analysis
Immunohistochemical analyses revealed that IRF-2 was mostly located in the cytoplasm and downregulated in human GC tissues compared with normal adjacent tissues (P < 0.001; Fig. 1A, B)
Summary
Interferon regulatory factor 2 (IRF-2) acts as an anti-oncogene in gastric cancer (GC); the underlying mechanism remains unknown. Gastric cancer (GC) is the fifth most frequent malignancy, with 1,000,000 new cases in 2018 worldwide [1]. An estimated 679,100 new cases have developed in China each year, making GC the second most deadly form of cancer in China [2]. The interferon regulatory factor (IRF) family in humans is a transcriptional factor that can modify gene expression by directly targeting the DNA promoter sequences of target genes [4]. IRF-2 is a crucial member of the IRF family, located on chromosome 4q34.1-q35.1; IRF-2 has no tissue specificity. It reportedly plays critical roles in oncogenesis, cell apoptosis, immune regulation, and cell differentiation. Further studies found that IRF-2 inactivation led to impaired
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