E74-like ETS transcription factor 1 promotes the progression of pancreatic cancer by regulating doublecortin-like kinase 1/Janus kinase/signal transducer and activator of transcription pathway.

This study was targeted at investigating the biological functions of E74-like ETS transcription factor 1 (ELF1) in pancreatic cancer (PC) and its underlying mechanism. ELF1 expression in PC tissues was detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Cell counting kit-8 (CCK-8) method, EdU method and flow cytometry were used to detect the cell proliferation and apoptosis of PC cell lines after transfection. A subcutaneous tumorigenesis model was constructed to validate the oncogenic role of ELF1 . PROMO database was used to predict the binding site of ELF1 on the promoter region of doublecortin-like kinase 1 (DCLK1). Dual-luciferase reporter gene assay, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assay and quantitative real-time PCR were performed to detect the binding of ELF1 to the promoter region of DCLK1. The effect of ELF1 on DCLK1 expression was detected by Western blot assay. It was found that ELF1 expression in PC tissues and cells was up-regulated. ELF1 overexpression promoted the proliferation and inhibited the apoptosis of PC cells, while knocking down ELF1 had the opposite effects. ELF1 could bind to the promoter region of DCLK1 and ELF1 overexpression promoted the expression of DCLK1. Bioinformatics analysis suggested that Janus kinase (JAK) - signal transducer and activator of transcription (STAT) signaling pathway was associated to DCLK1 expression, and overexpression of ELF1 promoted the expression of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). In conclusion, ELF1 promoted the malignant progression of PC via regulating DCLK1/ JAK/STAT signaling pathway.