Cargando…
MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin
Purpose: Several microRNAs (miRNAs) that are aberrantly expressed in glioblastoma multiforme (GBM) play a significant role in GBM formation and progression. The expression profile and functions of miR-559 in GBM remain unclear. Here, we quantified the expression and investigated the involvement of m...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556469/ https://www.ncbi.nlm.nih.gov/pubmed/31239710 http://dx.doi.org/10.2147/OTT.S202309 |
_version_ | 1783425331396345856 |
---|---|
author | Yang, Fan Zhang, Chuangang Xu, Congbin Fu, Fangyou Han, Dong Li, Hongliang |
author_facet | Yang, Fan Zhang, Chuangang Xu, Congbin Fu, Fangyou Han, Dong Li, Hongliang |
author_sort | Yang, Fan |
collection | PubMed |
description | Purpose: Several microRNAs (miRNAs) that are aberrantly expressed in glioblastoma multiforme (GBM) play a significant role in GBM formation and progression. The expression profile and functions of miR-559 in GBM remain unclear. Here, we quantified the expression and investigated the involvement of miR-559 in the oncogenicity of GBM cells in vitro and in vivo. Material and methods: Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was carried out to determine miR-559 expression in GBM tissues and cell lines. A series of functional assays was performed to evaluate the effects of miR-559 overexpression on GBM cell proliferation, apoptosis, migration, and invasion in vitro and on GBM tumor growth in vivo. The regulatory mechanisms of miR-559 action in GBM cells were then explored. Results: The expression of miR‑559 was lower in GBM tissues and cell lines and significantly correlated with the Karnofsky performance score and tumor size among patients with GBM. Exogenous miR‑559 expression inhibited GBM cell proliferation, migration, and invasion and promoted apoptosis. MiR-559 overexpression decreased tumor growth in vivo. Mechanistic experiments confirmed metadherin (MTDH) as a direct target gene of miR-559 in GBM. Silencing of MTDH induced effects similar to those of miR-559 upregulation in GBM cells, whereas MTDH expression restoration attenuated the antitumor effects of miR‑559 in GBM cells. Protein kinase B (AKT) in the phosphatase and tensin homolog (PTEN)–AKT signaling pathway was found to be deactivated in GBM cells after upregulation of miR-559 both in vitro and in vivo. Conclusion: MiR-559 acts as a tumor suppressor in GBM cells in vitro and in vivo, at least in part through the downregulation of MTDH and inhibition of AKT in the PTEN–AKT pathway. Therefore, targeting the miR-559–MTDH axis may be a promising therapeutic strategy for patients with GBM. |
format | Online Article Text |
id | pubmed-6556469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-65564692019-06-25 MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin Yang, Fan Zhang, Chuangang Xu, Congbin Fu, Fangyou Han, Dong Li, Hongliang Onco Targets Ther Original Research Purpose: Several microRNAs (miRNAs) that are aberrantly expressed in glioblastoma multiforme (GBM) play a significant role in GBM formation and progression. The expression profile and functions of miR-559 in GBM remain unclear. Here, we quantified the expression and investigated the involvement of miR-559 in the oncogenicity of GBM cells in vitro and in vivo. Material and methods: Reverse-transcription quantitative polymerase chain reaction (RT-qPCR) was carried out to determine miR-559 expression in GBM tissues and cell lines. A series of functional assays was performed to evaluate the effects of miR-559 overexpression on GBM cell proliferation, apoptosis, migration, and invasion in vitro and on GBM tumor growth in vivo. The regulatory mechanisms of miR-559 action in GBM cells were then explored. Results: The expression of miR‑559 was lower in GBM tissues and cell lines and significantly correlated with the Karnofsky performance score and tumor size among patients with GBM. Exogenous miR‑559 expression inhibited GBM cell proliferation, migration, and invasion and promoted apoptosis. MiR-559 overexpression decreased tumor growth in vivo. Mechanistic experiments confirmed metadherin (MTDH) as a direct target gene of miR-559 in GBM. Silencing of MTDH induced effects similar to those of miR-559 upregulation in GBM cells, whereas MTDH expression restoration attenuated the antitumor effects of miR‑559 in GBM cells. Protein kinase B (AKT) in the phosphatase and tensin homolog (PTEN)–AKT signaling pathway was found to be deactivated in GBM cells after upregulation of miR-559 both in vitro and in vivo. Conclusion: MiR-559 acts as a tumor suppressor in GBM cells in vitro and in vivo, at least in part through the downregulation of MTDH and inhibition of AKT in the PTEN–AKT pathway. Therefore, targeting the miR-559–MTDH axis may be a promising therapeutic strategy for patients with GBM. Dove 2019-06-05 /pmc/articles/PMC6556469/ /pubmed/31239710 http://dx.doi.org/10.2147/OTT.S202309 Text en © 2019 Yang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Yang, Fan Zhang, Chuangang Xu, Congbin Fu, Fangyou Han, Dong Li, Hongliang MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin |
title | MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin |
title_full | MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin |
title_fullStr | MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin |
title_full_unstemmed | MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin |
title_short | MicroRNA-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin |
title_sort | microrna-559 plays an inhibitory role in the malignant progression of glioblastoma cells by directly targeting metadherin |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556469/ https://www.ncbi.nlm.nih.gov/pubmed/31239710 http://dx.doi.org/10.2147/OTT.S202309 |
work_keys_str_mv | AT yangfan microrna559playsaninhibitoryroleinthemalignantprogressionofglioblastomacellsbydirectlytargetingmetadherin AT zhangchuangang microrna559playsaninhibitoryroleinthemalignantprogressionofglioblastomacellsbydirectlytargetingmetadherin AT xucongbin microrna559playsaninhibitoryroleinthemalignantprogressionofglioblastomacellsbydirectlytargetingmetadherin AT fufangyou microrna559playsaninhibitoryroleinthemalignantprogressionofglioblastomacellsbydirectlytargetingmetadherin AT handong microrna559playsaninhibitoryroleinthemalignantprogressionofglioblastomacellsbydirectlytargetingmetadherin AT lihongliang microrna559playsaninhibitoryroleinthemalignantprogressionofglioblastomacellsbydirectlytargetingmetadherin |