Micro-RNA29b enhances the sensitivity of glioblastoma multiforme cells to temozolomide by promoting autophagy.
Anat Rec (Hoboken)
; 304(2): 342-352, 2021 02.
Article
en En
| MEDLINE
| ID: mdl-32275350
ABSTRACT
To explore whether or not aberrant expression of miR-29b in glioblastoma multiforme (GBM) cells was associated with temozolomide (TMZ) resistance and to elucidate potential underlying mechanisms. Upregulation of miR-29 in GBM cells was achieved by transfecting miR-29b mimics. Changes in cell viability were measured by using CCK-8 assays. Flow cytometry and TUNEL assays were used to quantify the number of apoptotic cells. The expression levels of apoptosis-related proteins as well as autophagy-associated proteins, and the expression levels of both apoptotic and autophagic genes were determined by Western blotting. Autophagy flux was monitored by transfecting mRFP-GFP-LC3 adenovirus. We halted autophagy by introducing Atg 5-specific siRNA or the autophagy inhibitor Bafilomycin A1 (Baf-A1). We also employed a GBM xenograft mice model to confirm the role of miR-29b in vivo. miR-29b overexpression induced inhibition of cell viability, and also induced apoptosis and autophagy in U251 and U87MG cells. Furthermore, upregulation of miR-29b was able to potentiate the level of antitumor activity of TMZ against tested cells. We also found that autophagy induced by miR-29b, at least partially, contributed to the increase of TMZ sensitivity in GBM cells. As was evidenced by blockade of autophagy, the application of Atg 5 siRNA or Baf-A1 was able to significantly reverse these effects. Consistent with observations in vitro, findings of in vivo assessment also confirmed that overexpression of miR-29b was able to effectively halt tumor growth and enhance the antitumor activity of TMZ. miR-29b potentiates TMZ sensitivity against GBM cells by inducing autophagy and the combined use of miR-29 mimic and TMZ might represent a potential therapeutic strategy for GBM patients.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Autofagia
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Neoplasias Encefálicas
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Glioblastoma
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Antineoplásicos Alquilantes
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MicroARNs
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Temozolomida
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Anat Rec (Hoboken)
Asunto de la revista:
ANATOMIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
China