lncRNA MIR4435-2HG modulates the malignant progression of glioblastoma through the miR-181d-5p/MALT1/NF-κB signaling pathway

Glioblastoma (GBM) is a highly malignant brain tumor with a poor prognosis. Long noncoding RNAs (lncRNAs) significantly influence GBM pathogenesis. Although lncRNA MIR4435-2HG is known to promote tumorigenesis in various cancers, its regulatory role in GBM remains undefined. We quantified MIR4435-2HG and miR-181d-5p expression using quantitative reverse transcription polymerase chain reaction. The functional impact of the MIR4435-2HG/miR-181d-5p/MALT1/NF-κB axis was assessed in A172 and U87 MG cells through cell counting kit-8 (CCK-8), wound healing, Transwell, flow cytometry, Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), western blot, and immunofluorescence assays. Interactions between miR-181d-5p, MIR4435-2HG, and MALT1 were confirmed by dual-luciferase reporter, fluorescence in situ hybridization, RNA immunoprecipitation, and RNA pulldown experiments. Finally, a xenograft tumor model in C57BL/6 mice, combined with hematoxylin and eosin staining, immunohistochemistry, and TUNEL staining, was used to investigate the role of MIR4435-2HG in vivo. The results demonstrated that both MIR4435-2HG and MALT1 were upregulated in GBM tissues and cell lines, whereas the expression of miR-181d-5p was reduced. MIR4435-2HG promoted GBM cell proliferation and metastasis in both in vitro and in vivo experiments. Inhibition of MALT1 reversed the promotive effects of miR-181d-5p knock down on GBM cell proliferation and metastasis. Mechanistic studies revealed that MIR4435-2HG upregulates MALT1 expression and activates the NF-κB signaling pathway by sponging miR-181d-5p. In conclusion, MIR4435-2HG overexpression facilitates the malignant progression of GBM through the miR-181d-5p/MALT1/NF-κB pathway.