Reduced LINC00467 Elevates microRNA-125a-3p to Suppress Cisplatin Resistance in Non-Small Cell Lung Cancer Through Inhibiting Sirtuin 6 and Inactivating the ERK1/2 Signaling Pathway

Objective: Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as vital biomarkers in cancers. This study aimed to investigate effect of long intergenic non-protein coding RNA 467 (LINC00467)/miR-125a-3p/sirtuin 6 (SIRT6) axis on non-small cell lung cancer (NSCLC). Methods: Expression of LINC00467, miR-125a-3p, SIRT6 and the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway-related factors in NSCLC tissues and cells was determined. Parent cells A549 and H1299 were induced by cisplatin (DDP) to construct DDP resistant cell lines A549/DDP and H1299/DDP, and the drug resistance was verified. The DDP resistant cells were treated with relative plasmids to observe the impacts of altered LINC00467 and miR-125a-3p on biological processes and DDP resistance of cells. Results: LINC00467 and SIRT6 were upregulated, miR-125a-3p was suppressed and the ERK1/2 pathway was activated in NSCLC tissues and cells. Inhibited LINC00467 or elevated miR-125a-3p repressed malignant behaviors and DDP resistance of NSCLC cells. Depletion of miR-125a-3p reversed impacts of inhibited LINC00467 on NSCLC cells. Moreover, LINC00467 competitively bound to miR-125a-3p, and SIRT6 was targeted by miR-125a-3p. Conclusion: Reduced LINC00467 elevated miR-125a-3p to suppress DDP resistance in NSCLC cells by restricting SIRT6 and inactivating the ERK1/2 signaling pathway. This research may provide potential candidates for NSCLC chemotherapy. Funding Statement: The current work is funded by Research project of Health and Family Planning Commission of Heilongjiang Province.(Contract grant number: 2018268) and Research project of Health and Family Planning Commission of Heilongjiang Province. (Contract grant number: 2018416). Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: This study was approved and supervised by the animal ethics committee of The Affiliated Hospital of Guilin Medical University. The treatment of animals in all experiments conforms to the ethical standards of experimental animals. Written informed consents were acquired from all patients before this study. The protocol of this study was confirmed by the Ethic Committee of The Affiliated Hospital of Guilin Medical University and based on the ethical principles for medical research involving human subjects of the Helsinki Declaration.