LncRNA16 inhibits pyroptosis and promotes platinum resistance in non-small cell lung cancer by sponging miRNA1827 to regulate MBD3/GSDME expression.

BACKGROUND: Platinum-based chemotherapy is the standard first-line cancer treatment. However, patients experience relapses due to chemoresistance. We found that long non-coding RNA 16 (lncRNA16) promotes platinum resistance and inhibits cell death in non-small cell lung cancer (NSCLC). However, the type of cell death inhibited by lncRNA16 remains unknown. METHODS: The biological roles of lncRNA16 and microRNA 1827 (miRNA1827) in cell proliferation and colony formation were determined using functional experiments. Dual-luciferase reporter and RNA immunoprecipitation assays were performed to confirm the interactions between lncRNA16 and miRNA1827. In vivo patient-derived tumor xenograft (PDX) models were used to investigate the effects of miRNA1827 agomir on platinum resistance. RESULTS: Pyroptosis was inhibited in platinum-resistant NSCLC cells. LncRNA16 contributed to the expression of methyl-CpG binding domain protein 3 (MBD3) by sponging miRNA1827, thereby inhibiting gasdermin E (GSDME) expression, which inhibited pyroptosis in platinum-resistant NSCLC. The miRNA1827 agomir repressed platinum resistance in vitro experiments and in vivo PDX models. CONCLUSION: We identified a novel function of lncRNA16 in inhibiting pyroptosis and proposed an effective therapeutic drug, the miRNA1827 agomir, for chemosensitization. This study offers a potential strategy for treating patients with NSCLC, especially those with platinum resistance.