miR-149 rs2292832 C allele enhances the cytotoxic effect of temozolomide against glioma cells.
Alleles
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Brain Neoplasms
/ drug therapy
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Drug Resistance, Neoplasm
/ genetics
Female
Gene Expression Regulation, Neoplastic
/ drug effects
Glioma
/ drug therapy
Humans
Leukocytes
/ metabolism
Male
MicroRNAs
/ genetics
Neurons
/ drug effects
Prognosis
Temozolomide
/ pharmacology
Young Adult
Journal
Neuroreport
ISSN: 1473-558X
Titre abrégé: Neuroreport
Pays: England
ID NLM: 9100935
Informations de publication
Date de publication:
08 04 2020
08 04 2020
Historique:
entrez:
4
4
2020
pubmed:
4
4
2020
medline:
24
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32243354
doi: 10.1097/WNR.0000000000001440
pii: 00001756-202004010-00007
doi:
Substances chimiques
Antineoplastic Agents
0
MIRN149 microRNA, human
0
MicroRNAs
0
Temozolomide
YF1K15M17Y
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
498-506Références
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