The function and mechanism of LINC01583 on Osimertinib resistance in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer with a steady increase in incidence. This study aimed to confirm the role of LINC01583 on NSCLC progression and Osimertinib (Osi) resistance. The interactions of LINC01583, miR-4640-5p, and CHD8 were confirmed by RNA pulldown and Luciferase assay. The ROC curve was utilized to assess the discriminatory ability of LINC01583 for patients with Osi-resistant. Osi-sensitive NSCLC cell lines H1975 and PC9 were selected, and Osi-resistant cell lines were established by drug administration using the concentration gradient escalation method. The effect of LINC01583 on lung cancer drug-resistant cell lines was evaluated using CCK8, Transwell assay, and rescue experiments. In NSCLC cell lines and patients, the expression of LINC01583 and CHD8 was significantly increased, while miR-4640-5p expression was significantly decreased. Mechanistically, knockout of LINC01583 suppressed the migration ability of Osi-resistant cells and increased their sensitivity to Osi. Upregulation of LINC01583 can significantly promote the migration ability of lung cancer cell parent lines and reduce their sensitivity to Osi. Rescue experiments showed that co-transfection of miR-4640-5p inhibitor partially reversed the inhibitory effects of LINC01583 knockdown. LINC01583 acted as a molecular sponge for miR-4640-5p and regulated CHD8 expression by competitive binding. In this study, we revealed LINC01583 as a key oncogenic driver that promotes both NSCLC progression and Osi resistance by functioning as a ceRNA for miR-4640-5p, thereby upregulating its target gene CHD8. • LINC01583 is increased in NSCLC patients and cell lines. • Upregulation of LINC01583 in NSCLC cells promote the migration ability. • Upregulation of LINC01583 in NSCLC cells reduce their sensitivity to Osi. • Knockdown of LINC01583 in Osi-resistant cells inhibited the cell migration. • Knockdown of LINC01583 in Osi-resistant cells enhanced Osi sensitivity. • LINC01583 regulated CHD8 expression by sponging miR-4640-5p.