Association of Hsa_circ_0059511 with the sensitivity of the temozolomide chemotherapeutic treatment in human glioma cells

Abstract

Abstract While surgical resection combined with temozolomide (TMZ) chemotherapy remains the cornerstone of glioma treatment, therapeutic efficacy is significantly limited by intrinsic and acquired TMZ resistance. This study identified elevated expression of circular RNA circ0059511 in TMZ-resistant glioblastoma tissues and delineated its mechanistic role in chemoresistance. Circ0059511 silencing suppressed glioma cell proliferation, clonogenicity, and metastatic potential, as confirmed by Western blotting. These findings were corroborated in subcutaneous xenograft models, where circ0059511 silencing combined with TMZ reduced tumor volume. Mechanistically, circ0059511 functions as a competitive endogenous RNA that sequesters miR-194-5p, thereby derepressing FZD6 translation to sustain chemoresistance. Rescue experiments established the hierarchical regulatory axis: miR-194-5p inhibition and FZD6 ablation partially reversed the TMZ-sensitizing effects of circ0059511 knockdown. Our work unveils the circ0059511/miR-194-5p/FZD6 axis as a central mediator of TMZ resistance in glioblastoma, providing a rationale for combinatorial therapeutic strategies to overcome chemoresistance.

Keywords

• circ0059511
• Glioblastoma
• miR-194-5p
• Temozolomide resistance