GABRP inhibits the progression of oesophageal cancer by regulating CFTR: Integrating bioinformatics analysis and experimental validation

Abstract Oesophageal cancer (EC) is a malignancy which accounts for a substantial number of cancer‐related deaths worldwide. The molecular mechanisms underlying the pathogenesis of EC have not been fully elucidated. GSE17351 and GSE20347 data sets from the Gene Expression Omnibus (GEO) database were employed to screen differentially expressed genes (DEGs). Reverse transcription quantitative PCR (RT‐qPCR) was used to examine hub gene expression. ECA‐109 and TE‐12 cells were transfected using the pcDNA3.1 expression vector encoding GABRP . The cell counting kit‐8 (CCK‐8), cell scratch and Transwell assays were performed to assess the effect of GABRP on EC cell proliferation, migration and invasion. Epithelial‐mesenchymal transition (EMT)‐associated protein levels were measured by Western blotting. Subsequently, CFTR was knocked down to verify whether GABRP affected biological events in EC cells by targeting CFTR . Seven hub genes were identified, including GABRP , FLG , ENAH , KLF4 , CD24 , ABLIM3 and ABLIM1 , which all could be used as diagnostic biomarkers for EC. The RT‐qPCR results indicated that the expression levels of GABRP , FLG , KLF4 , CD24 , ABLIM3 and ABLIM1 were downregulated, whereas the expression level of ENAH was upregulated. In vitro functional assays demonstrated that GABRP overexpression suppressed the proliferation, migration, invasion and EMT of EC cells. Mechanistically, GABRP promoted the expression of CFTR , and CFTR knockdown significantly counteracted the influence of GABRP overexpression on biological events in EC cells. Overexpression of GABRP inhibited EC progression by increasing CFTR expression, which might be a new target for EC treatment.