Introduction: Non-small cell lung cancer (NSCLC), as the most common type of lung cancer, is a major therapeutic challenge. In recent years, the role of long non-coding RNAs (lncRNAs) in the pathogenesis of this disease has received attention. The aim of this study was to identify the target genes of lncRNAs and analyze their association with critical pathways and interaction networks related to NSCLC using bioinformatics approaches.
Methods: Sequencing samples from three individuals with early-stage LUSC non-small cell lung cancer (NSCLC) and three samples from adjacent non-cancerous tissues were downloaded from the NCBI public database. The data consisted of FASTQ files that were sequenced with an Illumina device. In the first step, the quality of the sequencing data was checked using FastQC software, and then the sequences were aligned with the human reference genome. Then, differential gene expression analysis was performed between patients and healthy individuals using DESeq2 software, and differentially expressed genes were identified based on statistical criteria (such as p-adjusted and log2 fold change). Disease-related lncRNAs were identified using GeneCards and RNAcentral databases. Then, functional enrichment analysis was performed using DAVID to identify biological pathways and cellular components. STRING was used to investigate protein-protein interactions (PPIs) and direct relationships with disease pathways. Finally, the central genes (hub genes) of the network were identified and analyzed using Cytoscape and the cytoHubba algorithm.
Results: The results of DAVID analysis showed that our target genes were significantly enriched in vital processes such as phosphorylation and transcriptional regulation and in cellular components such as the nucleus and cytoplasm. STRING analysis confirmed the direct association of 8 genes from our list with the non-small cell lung cancer pathway in the KEGG database and also showed their association with pathways such as the Ras signaling pathway. In addition, several central genes were identified as major control points in the PPI network, which are likely to play key roles in pathogenic processes.
Conclusion: This study provides a comprehensive bioinformatic view of the role of the studied lncRNAs in the pathogenesis of NSCLC. Our findings strengthen the hypothesis of their role in regulating key cancer-related pathways and introduce the identified central genes as valuable candidates for future experimental research and discovery of novel therapeutic targets. Furthermore, these insights pave the way for potential clinical applications, including the development of targeted therapies that could enhance treatment outcomes for patients suffering from this aggressive form of lung cancer. Continued exploration of these lncRNAs may unveil even more intricate mechanisms underlying tumor progression and resistance to existing therapies.