MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma

Abstract Background: Glioma is the most prevalent malignant tumor in human central nervous systems. Recently, the development of resistance to radiotherapy in glioma patients markedly vitiates the therapy outcome. MiR-153-3p has been reported to be closely correlated with tumor progression, but its...

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Autores principales: Sun,Deyu, Mu,Yi, Piao,Haozhe
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2018
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602018000100246
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spelling oai:scielo:S0716-976020180001002462019-06-24MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human gliomaSun,DeyuMu,YiPiao,Haozhe Glioma Radiosensitivity miR-153-3p BCL2 Abstract Background: Glioma is the most prevalent malignant tumor in human central nervous systems. Recently, the development of resistance to radiotherapy in glioma patients markedly vitiates the therapy outcome. MiR-153-3p has been reported to be closely correlated with tumor progression, but its effect and molecular mechanism underlying radioresistance remains unclear in glioma. Methods: The expression of miR-153-3p was determined in radioresistant glioma clinical specimens as well as glioma cell lines exposed to irradiation (IR) using quantitative real-time PCR. Cell viability, proliferation and apoptosis were then evaluated by MTT assay, colony formation assay, Flow cytometry analysis and caspase-3 activity assay in glioma cells (U87 and U251). Tumor forming was evaluated by nude mice model in vivo. TUNEL staining was used to detect cell apoptosis in nude mice model. The target genes of miR-153-3p were predicted and validated using integrated bioinformatics analysis and a luciferase reporter assay. Results: Here, we found that miR-153-3p was down-regulated in radioresistant glioma clinical specimens as well as glioma cell lines (U87 and U251) exposed to IR. Enhanced expression of miR-153-3p promoted the radiosensitivity, promoted apoptosis and elevated caspase-3 activity in glioma cells in vitro, as well as the radiosensitivity in U251 cell mouse xenografs in vivo. Mechanically, B cell lymphoma-2 gene (BCL2) was identified as the direct and functional target of miR-153-3p. Moreover, restoration of BCL2 expression reversed miR-153-3p-induced increase of radiosensitivity, apoptosis and caspase-3 activity in U251 cells in vitro. In addition, clinical data indicated that the expression of miR-153-3p was significantly negatively associated with BCL2 in radioresistance of glioma samples. Conclusions: Our findings suggest that miR-153-3p is a potential target to enhance the effect of radiosensitivity on glioma cells, thus representing a new potential therapeutic target for glioma.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.51 20182018-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602018000100246en10.1186/s40659-018-0203-6
institution Scielo Chile
collection Scielo Chile
language English
topic Glioma
Radiosensitivity
miR-153-3p
BCL2
spellingShingle Glioma
Radiosensitivity
miR-153-3p
BCL2
Sun,Deyu
Mu,Yi
Piao,Haozhe
MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma
description Abstract Background: Glioma is the most prevalent malignant tumor in human central nervous systems. Recently, the development of resistance to radiotherapy in glioma patients markedly vitiates the therapy outcome. MiR-153-3p has been reported to be closely correlated with tumor progression, but its effect and molecular mechanism underlying radioresistance remains unclear in glioma. Methods: The expression of miR-153-3p was determined in radioresistant glioma clinical specimens as well as glioma cell lines exposed to irradiation (IR) using quantitative real-time PCR. Cell viability, proliferation and apoptosis were then evaluated by MTT assay, colony formation assay, Flow cytometry analysis and caspase-3 activity assay in glioma cells (U87 and U251). Tumor forming was evaluated by nude mice model in vivo. TUNEL staining was used to detect cell apoptosis in nude mice model. The target genes of miR-153-3p were predicted and validated using integrated bioinformatics analysis and a luciferase reporter assay. Results: Here, we found that miR-153-3p was down-regulated in radioresistant glioma clinical specimens as well as glioma cell lines (U87 and U251) exposed to IR. Enhanced expression of miR-153-3p promoted the radiosensitivity, promoted apoptosis and elevated caspase-3 activity in glioma cells in vitro, as well as the radiosensitivity in U251 cell mouse xenografs in vivo. Mechanically, B cell lymphoma-2 gene (BCL2) was identified as the direct and functional target of miR-153-3p. Moreover, restoration of BCL2 expression reversed miR-153-3p-induced increase of radiosensitivity, apoptosis and caspase-3 activity in U251 cells in vitro. In addition, clinical data indicated that the expression of miR-153-3p was significantly negatively associated with BCL2 in radioresistance of glioma samples. Conclusions: Our findings suggest that miR-153-3p is a potential target to enhance the effect of radiosensitivity on glioma cells, thus representing a new potential therapeutic target for glioma.
author Sun,Deyu
Mu,Yi
Piao,Haozhe
author_facet Sun,Deyu
Mu,Yi
Piao,Haozhe
author_sort Sun,Deyu
title MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma
title_short MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma
title_full MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma
title_fullStr MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma
title_full_unstemmed MicroRNA-153-3p enhances cell radiosensitivity by targeting BCL2 in human glioma
title_sort microrna-153-3p enhances cell radiosensitivity by targeting bcl2 in human glioma
publisher Sociedad de Biología de Chile
publishDate 2018
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602018000100246
work_keys_str_mv AT sundeyu microrna1533penhancescellradiosensitivitybytargetingbcl2inhumanglioma
AT muyi microrna1533penhancescellradiosensitivitybytargetingbcl2inhumanglioma
AT piaohaozhe microrna1533penhancescellradiosensitivitybytargetingbcl2inhumanglioma
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