RNA sequencing uncovers the key long non-coding RNAs and potential molecular mechanism contributing to XAV939-mediated inhibition of non-small cell lung cancer

摘要

The present study aimed to reveal the key long non-coding RNAs (lncRNAs) and the potential molecular mechanisms of XAV939 treatment in non-small cell lung cancer (NSCLC). The NSCLC cell line, NCI-H1299, was cultured with 10 µM XAV939 for 12 h, and NCI-H1299 cells without XAV939 treatment were used as controls. Following RNA isolation from the two groups, RNA-sequencing was performed to detect transcript expression levels, and differentially-expressed lncRNAs (DE-lncRNAs) and DE-genes (DEGs) were identified between groups and analyzed for their functions and associated pathways. The potential associations between proteins encoded by DEGs were revealed via a protein-protein interaction (PPI) network. Subsequently, the microRNA (miRNA/miR)-mRNA, lncRNA-miRNA and lncRNA-mRNA interactions were explored, followed by competing endogenous RNA (ceRNA) network construction. A total of 396 DEGs and 224 DE-lncRNAs were identified between the XAV939 and control groups. These lncRNAs were mainly enriched in pathways such as ‘ferroptosis’ [DEG, solute carrier family 7 member 11 (SLC7A11)]. The PPI network consisted of 97 nodes and 112 interactions. Furthermore, a total of 10 noteworthy lncRNAs were revealed in the DE-lncRNA-DEG interaction. Finally, the lncRNA-miRNA-mRNA regulatory association, including MIR503 host gene (MIR503HG)-miR1273c-SRY-box 4 (SOX4), was explored in the current ceRNA network. The downregulation of lncRNA MIR503HG induced by XAV939 may serve an important role in NSCLC suppression via sponging miR-1273c and regulating SOX4 expression. Furthermore, the downregulation of SLC7A11 induced by XAV939 may also inhibit the development of NSCLC via the ferroptosis pathway.