Background: High expressions of lncRNA LINC00525 is linked to the progressive development of many cancers, including lung adenocarcinoma (LUAD). LncRNAs have regulatory roles in transcription and gene expression. Objectives: Investigation of the effect of LINC00525 knockdown on the transcriptome and signaling pathways of A549 LUAD cells was aimed for the first time in this study. Methods: Differentially expressed genes (DEGs) were obtained after LINC00525 silencing in A549 cells from the gene expression profile GSE171460. R packages were conducted to find enriched pathways. Hub genes were identified using PPI network based on STRING database. RNAInter and TRRUST databases were used to predict TFs that have interactions with LINC00525 and can regulate DEGs. Results: LINC00525 knockdown significantly changed the expression of approximately 3093 genes. The most significant enrichment pathways were cell cycle and cytokine signaling. All identified hub genes were upregulated. Many of them were related to cytokine signaling pathway, including STAT1, IL6, ISG15, IRF1, IRF7, IFIH1, and IFIT3. According to GEPIA database, decreased expression of LINC00525 showed a positive correlation with the increased expression of IL6, DDX58, IFIH1, OAS1, OAS2, and IFIT3 hub genes, which confirms the result of this study. Based on the transcription regulatory network, TFs of some DEGs and hub genes can have interactions with LINC00525. Conclusion: These findings are in line with the positive association between LINC00525 overexpression and tumor growth. LINC00525 may be a potential target for LUAD treatment. Further research is needed to investigate other functional mechanisms of LINC00525.
