LAUSR

OBJECTIVE The non-coding RNAs have been identified as potential biomarkers in cancers. This study aimed to investigate the effect of long intergenic non-protein coding RNA 467 (LINC00467)/microRNA (miR-125a-3p)/sirtuin 6 (SIRT6) axis on non-small cell lung cancer (NSCLC). METHODS Expression of LINC00467, miR-125a-3p, SIRT6, and ERK1/2 signaling pathway-related factor in NSCLC was assessed. A549 and H1299 cells were induced by cisplatin (DDP) to establish DDP-resistant cell lines, and the drug resistance was detected. DDP-resistant cells were transfected with relative oligonucleotides and/or plasmids to observe the effects of LINC00467 and miR-125a-3p on NSCLC cells. The interaction among LINC00467, miR-125a-3p, and SIRT6 was detected using dual luciferase reporter gene assay and RNA pull-down assay. A tumor xenograft model was established, and Ki67 expression was detected in tumors. RESULTS LINC00467 and SIRT6 were upregulated, miR-125a-3p was suppressed, and the ERK1/2 pathway was activated in NSCLC. LINC00467 or SIRT6 inhibition or miR-125a-3p elevation restricted malignancy and DDP resistance of NSCLC cells. Reduced miR-125a-3p reversed the effect of inhibited LINC00467 on NSCLC cells. LINC00467 competitively bound to miR-125a-3p, and miR-125a-3p targeted SIRT6. Inhibiting LINC00467 and SIRT6 or upregulating miR-125a-3p repressed tumor formation in vivo. CONCLUSION LINC00467 silencing upregulates miR-125a-3p to decrease DDP resistance in NSCLC cells via inhibiting SIRT6 and inactivating the ERK1/2 signaling pathway.