ABSTRACT
Background: Although the incidence of intrahepatic cholangiocarcinoma (CHOL) is low, the prognosis is very poor. The expression level of interleukin 23 receptor (IL23R) is linked to the occurrence and development of cancers. This study aimed to identify the role of IL23R in CHOL using bioinformatics tools and experimental validation. Methods: Circular RNA (circRNA), microRNA (miRNA), and messenger RNA (mRNA) datasets were obtained from the Gene Expression Omnibus (GEO) database, and R software was used for data analysis and visualization. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to conduct functional enrichment analysis, which was verified with gene set enrichment analysis software. Clinical data were obtained from The Cancer Genome Atlas (TCGA), and survival analyses were performed using the DriverDBv3 database and the Gene Expression Profiling Interactive Analysis website. The TIMER2.0 database provided us for immune cell infiltration analysis results of IL23R. Real-time quantitative polymerase chain reaction (RT-qPCR) was used for IL23R expression verification. Results: Differentially expressed (DE) mRNAs were enriched in phosphoinositide 3-kinase-serine/threonine kinase signaling pathway, immune-related tumor microenvironment (TME), and amino acid metabolism, etc. In addition, expression of IL23R was associated with immune infiltration-related cells. Furthermore, a circRNA-miRNA-IL23R network and a IL23R protein-protein interaction network were established. Most importantly, IL23R, as a prognostic gene, was found to have a low expression in CHOL. Conclusions: A circRNA-miRNA-IL23R network was identified, and it was found that IL23R may be a prognostic and immune-related biomarker in CHOL, which is worthy of further exploration.
ABSTRACT
Thyroid hormone receptor interactor 13 (TRIP13) plays a crucial role in poor prognosis and chemotherapy resistance of cancer patients. This present study is aimed at investigating the role of high expression of TRIP13 inducing nedaplatin (NDP) resistance in esophageal squamous cell carcinoma (ESCC) cells. High expression of TRIP13 promoted the proliferation and migration of ESCC cells performed by MTS assay, colony formation assay, wound healing assay, and transwell assay. High TRIP13 expression induced NDP resistance to ESCC based on the cell proliferation promoting/inhibition rate and cell migration promoting/inhibition rate analysis, flow cytometry assay of apoptotic subpopulations with a combination of Annexin V-FITC and propidium iodide, and Western blot analysis downregulating cleaved PARP, γH2A.X, cleaved caspase-3, and Bax and upregulating Bcl-2 expression. This study indicated that high expression of TRIP13 promoted proliferation and migration of ESCC cells and induced NDP resistance via enhancing repair of DNA damage and inhibiting apoptosis. This will provide a preliminary reference for the clinical use of NDP in ESCC treatment.
