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Brain Res Bull ; 163: 1-13, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32562719

RESUMEN

BACKGROUND: Glioma is a primary intracranial malignancy with poor prognosis, of which the pathogenesis remains to be elucidated. Therein, the aim of this study is to discuss the impacts of lncRNA plasmacytoma variant translocation 1 (PVT1)/microRNA-128-1-5p (miR-128-1-5p)/polypyrimidine tract-binding protein 1 (PTBP1) axis on the biological characteristics of glioma cells. METHODS: Glioma tissue samples (72 cases) and normal brain tissue samples (35 cases) were harvested. The expression of PVT1, miR-128-1-5p and PTBP1 in glioma tissues and cells was detected. Glioma cells were transfected with sh-PVT1, miR-128-1-5p mimics or miR-128-1-5p inhibitors to verify the impacts of PVT1 and miR-128-1-5p on DNA damage, cell colony formation, invasion, proliferation, migration and apoptosis of glioma U87 and U251 cells. The growth of transplanted tumor was tested by tumor xenograft in nude mice. The combination of PVT1 and miR-128-1-5p and the targeting relationship between miR-128-1-5p and PTBP1 were verified. RESULTS: PVT1 and PTBP1 expression was enhanced and miR-128-1-5p expression was degraded in glioma tissues and cells. Overexpressed miR-128-1-5p and lowly-expressed PVT1 promoted DNA damage, suppressed colony formation, invasion, proliferation and migration as well as boosted apoptosis of U251 and U87 cells. Up-regulating miR-128-1-5p and down-regulating PVT1 reduced transplanted tumor volume and weight of glioma in mice. Low expression miR-128-1-5p reversed the effect of low expression PVT1 on the biological characteristics of glioma cells. PVT1 specifically bound to miR-128-1-5p and PTBP1 was the target gene of miR-128-1-5p. CONCLUSION: This study suggests that down-regulated PVT1 or up-regulated miR-128-1-5p boosts apoptosis and attenuates proliferation of glioma cells by inhibiting PTBP1 expression. This study is essential for finding new therapeutic targets for glioma.


Asunto(s)
Apoptosis/fisiología , Neoplasias Encefálicas/metabolismo , Glioma/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/biosíntesis , MicroARNs/biosíntesis , Proteína de Unión al Tracto de Polipirimidina/biosíntesis , ARN Largo no Codificante/biosíntesis , Animales , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Proliferación Celular/fisiología , Células Cultivadas , Femenino , Regulación Neoplásica de la Expresión Génica/fisiología , Glioma/genética , Glioma/patología , Ribonucleoproteínas Nucleares Heterogéneas/antagonistas & inhibidores , Ribonucleoproteínas Nucleares Heterogéneas/genética , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Proteína de Unión al Tracto de Polipirimidina/antagonistas & inhibidores , Proteína de Unión al Tracto de Polipirimidina/genética , ARN Largo no Codificante/genética , Regulación hacia Arriba/fisiología , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
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