IL20RB promotes pancreatic cancer progression by activating NF- kB signalling and promoting EMT

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Abstract

Purpose Currently, the pathogenesis and biological features of pancreatic cancer are not fully understood. Interleukin-20 receptor subunit beta (IL20RB) is a risk factor for poor prognosis in a variety of solid tumours, including breast cancer. However, the biological characteristics of IL20RB in pancreatic cancer and its impact on patient prognosis remain unclear. The aim of this study was to investigate the effect of IL20RB on the biological characteristics of pancreatic cancer and to explore the underlying mechanisms. Methods The expression of IL20RB in pancreatic cancer and its effect on the prognosis of pancreatic cancer patients were analysed by The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Immunohistochemistry and Western blot were used to detect IL20RB expression in pancreatic cancer tissues. Pancreatic cancer cell lines PANC-1 and BxPC-3 with stable knockdown of IL20RB were constructed.The effects of IL20RB on the proliferation, migration, apoptosis and cell cycle of pancreatic cancer cells were analysed by CCK-8 assay, plate clone formation assay, wound healing assay, Transwell assay and flow cytometry. Transcriptome sequencing analysis and Western blot were used to detect changes in NF-κB signalling and key molecules during EMT after IL20RB knockdown. Results IL20RB is highly expressed in pancreatic cancer and that patients with high expression have a poor prognosis. Knockdown of IL20RB significantly inhibited the proliferation and migration of pancreatic cancer cells, induced cell apoptosis, and resulted in cell arrest in the S phase. Gene set enrichment analysis (GSEA) and transcriptome analysis showed that IL20RB regulated related signalling pathways in pancreatic cancer cells, including Nuclear factor-κb (NF-κB) and Epithelial-mesenchymal transition(EMT). After the knockdown of IL20RB, the expression of EMT-related protein E-cadherin was increased, and the expression of N-cadherin, Vimentin and Snail was decreased. At the same time, the expression levels of IKKα/β and P-NF-κB P65 were significantly reduced after IL20RB knockdown. The expression level of NF-κB P65 was not changed considerably, and the ratio of P-NF-κB P65/NF-κB P65 was significantly decreased. Conclusion IL20RB is highly expressed in pancreatic cancer and is associated with poor prognosis in patients. IL20RB may promote the proliferation, migration and apoptosis of pancreatic cancer cells by activating the IKKα/β/NF-κB P65 signalling pathway to promote the EMT process.

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