KDM2B promotes chemoresistance in glioma cells by inhibiting ferroptosis via the LINC01018/miR-182-5p axis

Glioma continues to pose significant challenges to clinicians worldwide. This study aims to explore the mechanism of lysine (K)-specific demethylase 2B (KDM2B) in chemoresistance in glioma cells through Ferroptosis and to identify new targets for glioma treatment. KDM2B, kruppel-like factor 9 (KLF9), long intergenic non-protein coding RNA 1018 (LINC01018), miR-182-5p, and six-transmembrane epithelial antigen of the prostate 2 (STEAP2) were detected in Cancer and adjacent tissues. Cell viability, half maximal inhibitory concentration (IC₅₀) values, and ferroptosis-related factors were measured in temozolomide (TMZ)-treated glioma cells. The enrichment of KDM2B, methylation of histone H3 lysine 36 (H3K36me1), and H3K36me2 on the KLF9 promoter and KLF9 on the LINC01018 promoter was analyzed. The bindings of KLF9 to LINC01018 and miR-182-5p to STEAP2 were detected. Inhibition of KLF9, LINC01018, or STEAP2 was combined with silencing KDM2B to verify the mechanism. KDM2B was highly expressed in glioma. KDM2B inhibition decreased the IC₅₀ of glioma cells to TMZ, which was reversed upon KDM2B overexpression. KDM2B inhibition promoted Ferroptosis in glioma cells. KDM2B inhibited KLF9 expression by removing H3K36me1/me2. KLF9 promoted LINC01018 expression, and LINC01018 increased STEAP2 expression by targeting miR-182-5p. Inhibition of KLF9, LINC01018, or STEAP2 partially reversed the promoting effects of KDM2B inhibition on Ferroptosis in glioma cells and increased cell resistance to TMZ. In conclusion, KDM2B promotes TMZ resistance in glioma cells by suppressing Ferroptosis via the KLF9/LINC01018/miR-182-5p/STEAP2 axis.

Chemoresistance; Ferroptosis; Glioma; KDM2B; KLF9.