LINC00968 and LINC00511 Regulate Gefitinib-Induced Proliferation Inhibition and Apoptosis and Drug Resistance-Related Genes in Non-Small-Cell Lung Cancer

Abstract

Background: Gefitinib is a first-line treatment option for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations. However, its effectiveness is limited due to unknown resistance mechanisms. The emergence of long non-coding RNAs (lncRNAs) has unveiled new insights into EGFR-tyrosine kinase inhibitor resistance. This study aimed to investigate the effects of LINC00968 and LINC00511 on NSCLC cells treated with gefitinib. Methods: We conducted high-throughput sequencing and enrichment analysis to screen potential target lncRNAs, and the expression levels of these lncRNAs were validated in cells using quantitative real-time PCR (qRT-PCR). The effects of LINC00968 overexpression or LINC00511 knockdown in gefitinib-treated cells on cell viability, proliferation, invasion, and apoptosis were determined using the Cell Counting Kit-8, clonogenesis, transwell, flow cytometry, and immunofluorescence. Additionally, western blotting was performed to detect alterations in the expression of drug-resistant proteins. Results: Transcriptome sequencing and verification in cell lines revealed that LINC00968 exhibited low expression levels in NSCLC cells, while LINC00511 exhibited high expression levels (p < 0.05). Overexpression of LINC00968 and knockdown of LINC00511 enhanced gefitinib-induced proliferation inhibition, invasion inhibition, and apoptosis in NSCLC cell lines (p < 0.05). In the si-LINC00511 and LINC00968 group, drug resistance-related genes, including multidrug resistance-associated protein 1, P-glycoprotein, low-density lipoprotein receptor-related protein 1, and hypoxia-inducible factor-1α, were upregulated. Furthermore, knockdown of LINC00511 and overexpression of LINC00968 elevated N-Cadherin expression while inhibiting E-Cadherin (p < 0.05). Conclusion: Our findings suggest that LINC00968 and LINC00511 regulate the sensitivity of NSCLC cells to gefitinib, potentially representing promising targets for improving the clinical efficacy of gefitinib.