LncRNA MEG3 inhibits glioma progression by inducing pyroptosis through the miR-223-3p/FOXO1/PARP1 axis.

Glioma, particularly glioblastoma (GBM), is a highly aggressive malignancy with limited therapeutic options. Pyroptosis, a pro-inflammatory regulated cell death, represents a promising tumor-suppressive mechanism; however, its precise regulatory networks in glioma remain incompletely defined. Although lncRNA MEG3 is a recognized tumor suppressor, whether it dictates glioma pyroptosis through a competing endogenous RNA (ceRNA) mechanism has yet to be characterized. In the study, we measured the expression profiles of MEG3, miR-223-3p, FOXO1 and PARP1 in glioma tissues and cultured cell lines. In vitro, we evaluated the biological effects of MEG3 modulation. Subcutaneous xenograft tumor models were established to investigate tumor progression in vivo. Dual-luciferase reporter and RIP assays validated the molecular interactions, and rescue experiments confirmed the functional importance of this axis. In comparison to normal counterparts, glioma specimens and cell models displayed a prominent reduction in MEG3 expression. Crucially, restoring MEG3 levels thwarted aggressive cellular traits (including proliferation, migration, and invasion) by prompting pyroptosis, a process validated by the elevated abundance of mature IL-1β, cleaved caspase-1, and GSDMD-N. Mechanistically, as a ceRNA molecule, MEG3 exerts its regulatory role by sponging and functionally neutralizing miR-223-3p, thus derepressing FOXO1 and PARP1 post-transcriptionally. Knockdown of FOXO1 or PARP1 effectively abrogated the pro-pyroptotic and anti-tumor effects induced by MEG3 overexpression. Consistently, MEG3 upregulation hindered tumor growth and triggered pyroptosis in vivo. In conclusion, our findings unveil a novel regulatory MEG3/miR-223-3p/FOXO1-PARP1 axis that drives pyroptosis to restrain glioma progression, which identifies this axis as a potential therapeutic target with translational value for glioma therapy.