Analysis of the lncRNA-miRNA-mRNA network reveals a potential regulatory mechanism of EGFR-TKIs resistance in NSCLC. Analysis of the lncRNA-miRNA-mRNA network reveals a potential regulatory mechanism of EGFR-TKIs resistance in NSCLC

In this study, to investigate the underlying molecular mechanisms of how EGFR-TKIs resistance occurs in NSCLC, we examined gene expression using microarray technology on gefitinib-resistant NSCLC cells to obtain differentially expressed (DE) lncRNAs and mRNAs. Then we carried out KEGG enrichment analysis for DE-mRNAs and constructed the ceRNA regulatory network of DE-lncRNAs and DE-mRNAs. Our results revealed the downregulated lncRNA LINC01128 acted as ceRNA to decrease PTEN via sponging miR-25-3p, and then the signal reactions caused by the reduction of PTEN would activate PI3K/Akt signaling pathway, which may lead to the development of drug resistance to EGFR-TKIs in NSCLC. Our findings will provide a novel perspective for the underlying molecular mechanisms of EGFR-TKIs resistance in NSCLC. Besides, this research will help to develop new therapeutic targets for EGFR-TKIs resistance in NSCLC. Overall design: gefitinib resistant PC-9 cells (G); gefitinib-sensitive PC-9 cells (P)