miR34a derived from mesenchymal stem cells stimulates senescence in glioma cells by inducing DNA damage.
Mol Med Rep
; 19(3): 1849-1857, 2019 Mar.
Article
en En
| MEDLINE
| ID: mdl-30592284
Insights into the roles of microRNAs (miRNAs/miRs) in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches in the treatment of glioma. miR34a, as a wellknown tumor suppressor miRNA, is closely related with cellular senescence. Mesenchymal stem cells (MSCs) are a major component of the tumor microenvironment and possess the ability to deliver exogenous miRs to glioma cells to exert antitumor effects. The present study investigated whether modified MSCs with miR34a possess an antitumor function in glioma cells. A Transwell system was used to coculture U87 glioma cells and MSCs overexpressing miR34a, and cell proliferation and senescence assessed. The expression of senescencerelated genes p53, Cdkn1a, and Cdkn2c were tested using reverse transcriptionquantitative polymerase chain reaction and protein expression levels of sirtuin 1 (SIRT1) and γH2A histone family, member X were detected by western blotting. Telomerase activity of U87 cells was examined using the Telo TAGGG Telomerase PCR ELISA PLUS kit. The results demonstrated that the delivered exogenous miR34a from MSCs significantly decreased expression of the target gene SIRT1. In addition, the delivered miR34a decreased the proliferation of glioma cells and provoked the expression of senescencerelated genes p53, Cdkn1a, and Cdkn2c. In addition, upregulation of miR34a induced DNA damage, shortened telomere length and impaired telomerase activity. However, these prosenescent effects were reversed by forced SIRT1 upregulation. In conclusion, the results demonstrated a novel role for miR34a, inducing glioma cell senescence, whereas miR34a modulation of SIRT1, inducing DNA damage, is crucial for miRNA replacement therapy in glioma treatment.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
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Neoplasias Encefálicas
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Senescencia Celular
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MicroARNs
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Células Madre Mesenquimatosas
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Glioma
Límite:
Humans
Idioma:
En
Revista:
Mol Med Rep
Año:
2019
Tipo del documento:
Article