Identifying circRNA-miRNA-mRNA Networks Associated with Osimertinib Resistance in Lung Adenocarcinoma by Analyzing Microarray Datasets

<b>Background: </b>This study was to screen for circRNAs associated with osimertinib resistance in lung adenocarcinoma (LUAD) and establish a circRNA-miRNA-mRNA ceRNA network. <b>Methods:</b> DESeq2 analysis was used to identify circRNAs in GEO database associated with osimertinib resistance in LUAD. Differentially expressed miRNAs in LUAD intersected with the target miRNAs of circRNA. Predicted target gene for miRNAs were overlapped with the co-expressed genes of EGFR. Hsa_circ_0078465/miR-183-5p/NRAS axis was validated in cells. <b>Results:</b> Osimertinib resistance-related circRNAs in LUAD were linked to six differentially expressed miRNAs and 35 EGFR-related mRNAs. NRAS was the hub gene. These mRNAs were associated with cell motility regulation, non-small cell lung cancer and EGFR tyrosine kinase inhibitor resistance pathway. The cell proliferation and migration assays confirmed the promoting role of hsa_circ_0078465/miR-183-5p/NRAS axis in osimertinib-resistant cells. <b>Conclusion:</b> A circRNA-miRNA-mRNA network associated with osimertinib resistance in LUAD proposed hsa_ circ_0078465/miR-183-5p/NRAS axis.