Background and aimsGastric intestinal metaplasia (IM) is common in the gastric epithelium of patients with chronic atrophic gastritis. CDX2 activation in IM is driven by reflux of bile acids and following chronic inflammation. But the mechanism underlying how bile acids activate CDX2 in gastric epithelium has not been fully explored.MethodsWe performed microRNA (miRNA) and messenger RNA (mRNA) profiling using microarray in cells treated with bile acids. Data integration of the miRNA/mRNA profiles with gene ontology (GO) analysis and bioinformatics was performed to detect potential miRNA-mRNA regulatory circuits. Transfection of gastric cancer cell lines with miRNA mimics and inhibitors was used to evaluate their effects on the expression of candidate targets and functions. Immunohistochemistry and in situhybridisation were used to detect the expression of selected miRNAs and their targets in IM tissue microarrays.ResultsWe demonstrate a bile acids-triggered pathway involving upregulation of miR-92a-1–5p and suppression of its target FOXD1 in gastric cells. We first found that miR-92a-1–5p was increased in IM tissues and induced by bile acids. Moreover, miR-92a-1–5p was found to activate CDX2 and downstream intestinal markers by targeting FOXD1/FOXJ1 axis and modulating activation of nuclear factor kappa B (NF-κB) pathway. Furthermore, these effects were found to be clinical relevant, as high miR-92a-1–5p levels were correlated with low FOXD1 levels and high CDX2 levels in IM tissues.ConclusionThese findings suggest a miR-92a-1–5p/FOXD1/NF-κB/CDX2 regulatory axis plays key roles in the generation of IM phenotype from gastric cells. Suppression of miR-92a-1–5p and restoration of FOXD1 may be a preventive approach for gastric IM in patients with bile regurgitation.
Non-small cell lung cancer is one of the most common types of malignances worldwide and the main cause of cancer-related deaths. Current treatment for NSCLC is based on surgical resection, chemotherapy, radiotherapy, and targeted therapy, with poor therapeutic effectiveness. In recent years, immune checkpoint inhibitors have applied in NSCLC treatment. A large number of experimental studies have shown that immune checkpoint inhibitors are safer and more effective than traditional therapeutic modalities and have allowed for the development of better guidance in the clinical treatment of advanced NSCLC patients. In this review, we describe clinical trials using ICI immunotherapies for NSCLC treatment, the available data on clinical efficacy, and the emerging evidence regarding biomarkers.
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