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Background: Patients with non‐small cell lung cancer (NSCLC) are diagnosed in advanced stages and with a poor 5‐year survival rate. There is a critical need to identify novel biomarkers to improve the therapy and overall prognosis of this disease. Methods: Differentially expressed genes (DEGs) were identified from three profiles of GSE101586, GSE101684 and GSE112214 using Venn diagrams. hsa_circ_0043256 were validated using quantitative real‐time polymerase chain reaction (RT‐qPCR). The circular RNA–microRNA–messenger RNA (circRNA–miRNA–mRNA) regulatory network was constructed with Cytoscape 3.7.0. Hub genes were identified with protein interaction (PPI) and validated with the Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA) databases, and immunohistochemistry. Survival analyses were also performed using a Kaplan–Meier (KM) plotter. The effects of hsa_circ_0043256 on cell proliferation and cell cycles were evaluated by EdU staining and flow cytometry, respectively. Results: hsa_circ_0043256, hsa_circ_0029426 and hsa_circ_0049271 were obtained. Following RT‐qPCR validation, hsa_circ_0043256 was selected for further analysis. In addition, functional experiment results indicated that hsa_circ_0043256 could inhibit cell proliferation and cell‐cycle progression of NSCLC cells in vitro. Prediction by three online databases and combining with DEGs identified from The Cancer Genome Atlas (TCGA), a network containing one circRNAs, three miRNAs, and 209 mRNAs was developed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated DEGs might be associated with lung cancer onset and progression. A PPI network based on the 209 genes was established, and five hub genes (BIRC5, SHCBP1, CCNA2, SKA3, and GINS1) were determined. Following verification of five hub genes using GEPIA database, HPA database, and immunohistochemistry. High expression of all five hub genes led to poor overall survival. Conclusion: Our study constructed a circRNA–miRNA–mRNA network of hsa_circ_0043256. hsa_circ_0043256 may be a potential therapeutic target for lung cancer. [ABSTRACT FROM AUTHOR]

Background: With the ongoing development of targeted therapy and immunotherapy in recent years, the overall five‐year survival rate of NSCLC patients has not improved, and the search for novel diagnostic and prognostic markers for lung adenocarcinoma continues. Methods: Lung adenocarcinoma (LUAD) gene expression data and relevant clinical information were obtained from the TCGA. Hub genes were identified with weighted gene co‐expression network analysis (WGCNA) and protein–protein interaction network (PPI). Survival analyses were also performed using GEPIA. The 536 LUAD patients were divided into two groups according to the SPRR1B expression level and analyzed by gene set enrichment analysis (GSEA) and verified by immunoblotting. The effects of SPRR1B on cell proliferation and cell metastasis and apoptosis were evaluated by 5‐ethynyl‐2′‐deoxyuridine (EdU) staining, colony formation assay, transwell migration and invasion assay, and flow cytometry, respectively. Results: A total of 2269 DEGs were analyzed by WGCNA and five hub genes (CCK, FETUB, PCSK9, SPRR1B, and SPRR2D) were identified. Among them, SPRR1B was selected as one of the most significant prognostic genes in LUAD. SPRR1B was found to be highly expressed in lung adenocarcinoma cells compared with that in normal bronchial epithelial cells. In addition, silencing of SPRR1B could inhibit the cell proliferation, invasion, and migration of lung adenocarcinoma cells, but induced cell apoptosis and G2/M phase arrest in vitro. The result of GSEA and immunoblotting revealed that SPRR1B activated the MAPK signaling pathway involved in the proliferation and metastasis of lung cancer. Conclusions: Our findings demonstrate that SPRR1B may function as a prognosis predictor in lung adenocarcinoma. [ABSTRACT FROM AUTHOR]