miR-149 rs2292832 C allele enhances the cytotoxic effect of temozolomide against glioma cells
| Autor: | Qingchang Liu, Gengqiang Ling, Xinjie Ning, Juncheng Luo, Jian Guo, Binchu Xu, Xinlin Luo |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cell Survival Antineoplastic Agents Apoptosis Young Adult 03 medical and health sciences 0302 clinical medicine SOX2 Cell Line Tumor Glioma Leukocytes Temozolomide medicine Humans Cytotoxic T cell Allele Cytotoxicity Alleles Cell Proliferation Neurons biology Brain Neoplasms business.industry General Neuroscience Transfection Prognosis medicine.disease Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Drug Resistance Neoplasm biology.protein Cancer research Female Cyclin-dependent kinase 6 business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | NeuroReport. 31:498-506 |
| ISSN: | 0959-4965 |
| DOI: | 10.1097/wnr.0000000000001440 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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