Alteration in the level of NR2F2-AS1/ miR-320b / BMI1 differentially converges with the progression of gastric adenocarcinoma toward metastasis

Abstract

Abstract A regulatory pathway centered on lncRNA NR2F2-AS1/miR20b effects on dysregulation of BMI1 was hypothesized particularly in higher stages, which was confirmed by our bioinformatics examinations. An increase of more than 2-fold for BMI-1 and lncRNA NR2F2-AS1, respectively found in lower stages, and elevation continued with the increasing stage of the disease, and converged with significant downregulation of miR-320b and PTEN, noticing their association with tumor progression and decreased patient survival. lncRNA NR2F2-As1 acts as an oncogene to sponge miR-320b making changes in BMI1. A reduction in the amount of miR-320b against lncRNA NR2F2-AS1 and BMI1 directly correlates with a reduced overall survival rate of patients, especially if this disproportion is more than 3.0. Further study by gene ontology and KEGG pathway enrichment analysis revealed that disruption in the expression of BMI1 interplays in WNT, AKT, and RTK pathways affected the cell cycle, and provide the condition in favor of tumor progression. ROC curve analysis indicated that alteration in the level of BMI1 and lncRNA NR2F2-AS1 showed more than 94.0% sensitivity and specificity to differentiate the lower from higher stages of GC and predict the early onset of metastasis. This study can suggest another molecular aspect in the pathogenesis or prognostic marker for the progression of GC, particularly if this event is also observed in the blood of the patients.