Abstract: Objective: To elucidate the mediating role and preliminary mechanism of the long non-coding RNA (lncRNA) LINC01430 in the inhibitory effect of sanguinarine on non-small cell lung cancer (NSCLC).
Methods: Differentially expressed lncRNAs in NSCLC cells (A549 and H1975) before and after sanguinarine treatment were identified by high-throughput lncRNA sequencing. Public databases combined with RT-qPCR were used to assess LINC01430 expression in NSCLC tissues and cell lines and its prognosis. A LINC01430-overexpressing A549 cell model was established to evaluate the effects of sanguinarine on cell proliferation, apoptosis, and the expression of downstream genes (NOX4 and IL-6) by CCK-8, TUNEL, RT-qPCR and Western blot assays.
Results: A total of 361 differentially expressed lncRNAs were identified after sanguinarine treatment. Among them, LINC01430 was significantly downregulated (P < 0.001), accompanied by decreased mRNA levels of oxidative stress and inflammation-related target genes NOX4 and IL-6 (P < 0.05, P < 0.01). LINC01430 exhibited high expression in both NSCLC tissues and cell lines (P < 0.05) and was associated with poorer prognosis (HR = 1.15). Overexpression of LINC01430 significantly attenuated the anti-tumor effects of sanguinarine on NSCLC cell proliferation and apoptosis (P < 0.05) and partially reversed the downregulation of NOX4 and IL-6 by sanguinarine.
Conclusion: Sanguinarine may inhibit NSCLC by downregulating LINC01430 and its downstream NOX4/IL-6 axis. LINC01430 may serve as a potential therapeutic target for NSCLC.