miR-149 rs2292832 C allele enhances the cytotoxic effect of temozolomide against glioma cells

Glioma is a common cancer that affects people worldwide with high morbidity and mortality. Human miR-149 rs2292832 C/T polymorphism and miR-149-5p expressions have been documented to play important roles in various type of cancers. This study aims to assess the impact of miR-149 rs2292832 C/T polymorphism and miR-149-5p expressions in cytotoxic effect of temozolomide against glioma cells. A total of 137 cases of glioma patients and 21 healthy cases were enrolled in this study for clinical research. We found that miR-149-5p was significantly downregulated in glioma cell lines and in blood leukocyte of glioma patients. Furthermore, miR-149 rs2292832 C/T polymorphism was significantly associated with glioma prognosis and temozolomide resistance. Subsequently, the glioma cell lines stable transfected with common miR-149 expression construct (miR-149-T) and the variant miR-149 expression construct (miR-149-C) were used to determine the regulatory effect of miR-149 rs2292832 C on glioma cells progression. Data revealed that miR-149 rs2292832 C allele could enhance the miR-149-5p expressions, and therefore, prevent the proliferation of glioma cells and increase the cytotoxicity of temozolomide against glioma cells. These functions of miR-149-C were demonstrated to be triggered by CDK6/SOX2 pathway inhibition. The above results demonstrated that miR-149 rs2292832 C/T polymorphism was a potential prognostic biomarker for glioma development by regulating miR-149/CDK6 axis.