LAUSR

Aims: The acquired drug resistance has been regarded as a main barrier for the effective treatment of temozolomide (TMZ) in glioblastoma (GBM). MiR‐126‐3p is commonly down‐regulated and exerts tumor‐suppressive roles in kinds of human cancers, including GBM. This study was designed to investigate the functions and mechanisms of miR‐126‐3p in regulating TMZ resistance in GBM. Materials and methods: qRT‐PCR analysis was used to measure the expressions of miR‐126‐3p and SOX2 mRNA in GBM tissues and cells. Cell viability, colony forming ability and apoptosis were detected to evaluate the effect of miR‐126‐3p or SOX2 on TMZ resistance. Luciferase reporter experiments were applied to identify the target genes of miR‐126‐3p. Western blot analysis was performed to determine the protein levels associated with Wnt/&bgr;‐catenin signaling. TOP/FOP Flash assays were conducted to determine the effects of miR‐126‐3p or SOX2 on Wnt/&bgr;‐catenin signaling. Key findings: miR‐126‐3p expression was decreased in TMZ‐resistant GBM tissues and cells. High levels of miR‐126‐3p enhanced TMZ sensitivity by inhibiting cell viability, reducing colony forming potential and inducing apoptosis. Additionally, SOX2 was identified as a downstream target of miR‐126‐3p. On the contrary, SOX2 overexpression conferred TMZ resistance of GBM cells. Moreover, miR‐126‐3p‐mediated TMZ sensitivity was reversed following increased expression of SOX2. Furthermore, miR‐126‐3p‐induced inactivation of Wnt/&bgr;‐catenin signaling was greatly abrogated by SOX2 up‐regulation. Significance: MiR‐126‐3p sensitizes GBM cells to TMZ possibly by repressing SOX2 expression and blocking Wnt/&bgr;‐catenin signaling. This study provides novel targets to overcome TMZ resistance in GBM chemotherapy.