Down-regulation of interferon regulatory factor 2 binding protein 2 suppresses gastric cancer progression by negatively regulating connective tissue growth factor

Abstract

Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional repressor involved in regulating gene expression and other biological processes, including tumorigenesis. However, the clinical significance and roles of IRF2BP2 in human gastric cancer (GC) remain uncertain. Clinical GC tissues were obtained from GC patients at the First Affiliated Hospital of Nanchang University. Immunohistochemistry (IHC) was conducted to detect the IRF2BP2 protein in clinical paraffin specimens. Cell proliferation, migration and invasion were evaluated by MTT, colony formation assays and transwell assays. Co-immunoprecipitation was conducted to detect the interaction between TEA domain family members 4 (TEAD4) and vestigial-like family member 4 (VGLL4) or Yes-associated protein 1 (YAP1). Dual-luciferase reporter assay was used to confirm the binding of miR-101-3p to the 3'-UTR. The expression of IRF2BP2 was significantly higher in GC tissues than in normal tissues. Patients with higher IRF2BP2 protein expression had lower survival. IRF2BP2 knockdown inhibited proliferation, migration, invasion and epithelial-mesenchymal transition in GC cells. IRF2BP2 knockdown decreased the mRNA and protein levels of connective tissue growth factor (CTGF). The interaction between IRF2BP2 and VGLL4 increased the binding of TEAD4 to YAP1, resulting in the transcriptional coactivation of CTGF. In addition, miR-101-3p suppressed the expression of CTGF by directly targeting the 3'-UTR of IRF2BP2. Taken together, these findings provide a model for the role of miR-101-3p-IRF2BP2-CTGF signalling axis in GC and a novel insight into the mechanism of GC progression and metastasis.

Keywords: IRF2BP2; connective tissue growth factor; gastric cancer; prognosis.