Lung adenocarcinoma (LUAD) is one of the most common malignancies, and there is still a lack of effective biomarkers for early detection and prognostic prediction. Here, we comprehensively analyze the characteristics of. an RNA sequencing data set of LUAD samples. In total, 395 long non-coding RNAs (lncRNAs), 89 microRNAs (miRNAs), and 872 mRNAs associated with c-Myc were identified, which were differentially expressed between tumor and normal tissues. The most relevant pathway was found to be WT1-AS–miR-200a-3p–IGF2BP2 according to the rules of competitive endogenous RNA (ceRNA) regulation. WT1-AS and IGF2BP2 expression were positively correlated and increased in LUAD samples, while miR-200a-3p had relatively low expression. The high expression of WT1-AS and IGF2BP2 was associated with poor prognosis in LUAD patients, while low expression of miR-200a-3p predicted reduced survival (p < 0.05). The analysis of the multi-gene regulation model indicated that the WT1-AS (downregulation)–miR-200a-3p (upregulation)–IGF2BP2 (downregulation) pattern significantly improved the survival of LUAD patients. Finally, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were detected in LUAD cells, and the results are consistent with the bioinformatics analysis. In summary, the WT1-AS/IGF2BP2 axis is a potential prognostic biomarker in LUAD and is expected to become an effective target for diagnosis and treatment.

Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide, and effective biomarkers are still lacking for early detection and prognosis prediction. Here, based on gene expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA), 806 long non-coding RNAs (lncRNAs), 122 microRNAs (miRNAs) and 1269 mRNAs associated with CDK1 were identified. The regulatory axis of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT was determined according to the correlation between gene expression and patient prognosis. The abnormal up-regulation of FAM111B/ZWINT in LUAD was related to hypomethylation. Furthermore, immune infiltration analysis suggested FAM111B/ZWINT could affect the development and prognosis of cancer by regulating the LUAD immune microenvironment. EMT feature analysis suggested that FAM111B/ZWINT promoted tumor spread through the EMT process. Functional analysis showed FAM111B/ZWINT was involved in cell cycle events such as DNA replication and chromosome separation. We analyzed the HERB and GSCALite databases to identify potential target medicines that may play a role in the treatment of LUAD. Finally, the expression of LINC00460/LINC00525-hsa-mir-338-FAM111B/ZWINT axis was verified in LUAD cells by RT-qPCR, and these results were consistent with bioinformatics analysis. Overall, we constructed a CDK1-related ceRNA network and revealed the LINC00460/LINC00525-hsa-mir-338-FAM111/ZWINT pathways as potential diagnostic biomarkers or therapeutic targets of LUAD.

Background: Lung adenocarcinoma (LUAD) is one of the most aggressive and lethal tumor types and requires effective diagnostic and therapeutic targets. Though the epidermal growth factor receptor (EGFR) is an important target for LUAD therapy, acquired resistance is still inevitable. In recent years, the regulation of the EGFR by competing endogenous RNAs (ceRNAs) has been extensively studied and significant progress has been made. Therefore, we aim to find new targets for the diagnosis and treatment of LUAD by analyzing the EGFR-related ceRNA network in LUAD and expect to address the problem of EGFR resistance. Methods: We identified differentially expressed lncRNAs, miRNAs and mRNAs closely associated with the EGFR by analyzing transcriptome data from LUAD samples. Comprehensive bioinformatics analysis strongly suggests that the LINC00460—mir-338-3p—MCM4 ceRNA network plays an important role in the diagnosis and prognosis of LUAD. The effects of different patterns of the LINC00460/MCM4 axis on the overall survival of patients with LUAD were analyzed by a polygene regulation model. We also verified the expression of these genes in LUAD cell lines and tumor tissues by RT-PCR and immunohistochemistry. The functional enrichment analysis and targeted drug prediction of the MCM4 gene were performed. Results: Survival analysis indicated that high expressions of LINC00460 and MCM4 predict a shorter survival period for patients. Univariate and multivariate regression analyses demonstrated that higher expressions of LINC00460 and MCM4 were significantly associated with tumor size, lymph node metastasis, distant metastasis and TNM stage. A multi-gene regulation model analysis revealed that the LINC00460 (downregulation)—mir-338-3p (upregulation)—MCM4 (downregulation) pattern significantly improved the overall survival of LUAD patients (p = 0.0093). RT-PCR and immunohistochemical experiments confirmed our analytical results. In addition, the functional enrichment analysis indicated that MCM4-related genes were mainly enriched in the cell cycle and cell division. A functional association network analysis showed that MCM4 was closely related to the EGFR. Finally, the possible targeted drugs of MCM4 were queried through the drug database platform, hoping to solve its drug resistance problem by targeting EGFR-related genes. Conclusions: In summary, the LINC00460/MCM4 axis can be used as a potential new perspective for targeting EGFR genes in precision medicine and is expected to serve as a diagnostic, prognostic and drug target for LUAD.