LncRNA16 inhibits pyroptosis and promotes platinum resistance in non-small cell lung cancer by sponging miRNA1827 to regulate MBD3/GSDME expression
Abstract 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). Howev...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-025-03812-z |
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| Summary: | Abstract 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. |
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| ISSN: | 1475-2867 |