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Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling
Glioblastoma is the most common malignant brain tumor in adults and is characterized by extensive proliferation and the diffused invasion of tumor cells. Due to the intricate signaling pathways involved in glioma progression, more effective targeted therapies and prognostic biomarkers in clinical pr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746316/ https://www.ncbi.nlm.nih.gov/pubmed/29115407 http://dx.doi.org/10.3892/ijmm.2017.3233 |
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author | Gu, Jian-Jun Fan, Kai-Chun Zhang, Jian-He Chen, Hong-Jie Wang, Shou-Sen |
author_facet | Gu, Jian-Jun Fan, Kai-Chun Zhang, Jian-He Chen, Hong-Jie Wang, Shou-Sen |
author_sort | Gu, Jian-Jun |
collection | PubMed |
description | Glioblastoma is the most common malignant brain tumor in adults and is characterized by extensive proliferation and the diffused invasion of tumor cells. Due to the intricate signaling pathways involved in glioma progression, more effective targeted therapies and prognostic biomarkers in clinical practice are required. The suppression of proto-oncogene function or recovery of tumor suppressor gene function remains one of the primary approaches in gene therapy. The close association between the abnormal expression or mutation of microRNA (miRNA) and the tumorigenesis, progression and staging in glioma have been demonstrated previously. However, the expression pattern and specific role of microRNA-130b (miR-130b) in the tumor occurrence and progression of glioma are unclear. In the present study, quantitative polymerase chain reaction was performed to determine the expression level of miR-130b in 30 brain glioma patients and 3 glioma cell lines. An miR-130b inhibitor was transfected into U87 cells to downregulate the expression of miR-130b, and assessments of cell proliferation, cell cycle, apoptosis, cell invasion and migration in vitro and nude mouse tumorigenicity in vivo were conducted. Western blotting and luciferase reporter gene technology were used to verify the downstream target gene of miR-130b, namely phosphatase and tensin homolog (PTEN). The results demonstrated that miR-130b expression was increased in glioma tissues and cell lines in comparison with non-glioma tissues or cells. The downregulated expression of miR-130b inhibited the proliferation and invasion of glioma cells, induced apoptosis of the cells in vitro and inhibited their tumorigenicity in vivo. Western blotting and luciferase reporter assays demonstrated that the PTEN gene is a direct target of miR-130b. Western blotting revealed that the miR-130b inhibitor upregulated the expression of PTEN, inhibited AKT pathway activation, upregulated the tumor suppressor gene p27, and suppressed cyclin D1, matrix metalloproteinase 2 and 9 expression. These results suggest that the miR-130b inhibitor suppressed glioma cell proliferation and invasion via the PTEN/AKT pathway. Therefore, miR-130b is suggested to be an effective therapeutic target for glioma. |
format | Online Article Text |
id | pubmed-5746316 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-57463162017-12-31 Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling Gu, Jian-Jun Fan, Kai-Chun Zhang, Jian-He Chen, Hong-Jie Wang, Shou-Sen Int J Mol Med Articles Glioblastoma is the most common malignant brain tumor in adults and is characterized by extensive proliferation and the diffused invasion of tumor cells. Due to the intricate signaling pathways involved in glioma progression, more effective targeted therapies and prognostic biomarkers in clinical practice are required. The suppression of proto-oncogene function or recovery of tumor suppressor gene function remains one of the primary approaches in gene therapy. The close association between the abnormal expression or mutation of microRNA (miRNA) and the tumorigenesis, progression and staging in glioma have been demonstrated previously. However, the expression pattern and specific role of microRNA-130b (miR-130b) in the tumor occurrence and progression of glioma are unclear. In the present study, quantitative polymerase chain reaction was performed to determine the expression level of miR-130b in 30 brain glioma patients and 3 glioma cell lines. An miR-130b inhibitor was transfected into U87 cells to downregulate the expression of miR-130b, and assessments of cell proliferation, cell cycle, apoptosis, cell invasion and migration in vitro and nude mouse tumorigenicity in vivo were conducted. Western blotting and luciferase reporter gene technology were used to verify the downstream target gene of miR-130b, namely phosphatase and tensin homolog (PTEN). The results demonstrated that miR-130b expression was increased in glioma tissues and cell lines in comparison with non-glioma tissues or cells. The downregulated expression of miR-130b inhibited the proliferation and invasion of glioma cells, induced apoptosis of the cells in vitro and inhibited their tumorigenicity in vivo. Western blotting and luciferase reporter assays demonstrated that the PTEN gene is a direct target of miR-130b. Western blotting revealed that the miR-130b inhibitor upregulated the expression of PTEN, inhibited AKT pathway activation, upregulated the tumor suppressor gene p27, and suppressed cyclin D1, matrix metalloproteinase 2 and 9 expression. These results suggest that the miR-130b inhibitor suppressed glioma cell proliferation and invasion via the PTEN/AKT pathway. Therefore, miR-130b is suggested to be an effective therapeutic target for glioma. D.A. Spandidos 2018-01 2017-11-02 /pmc/articles/PMC5746316/ /pubmed/29115407 http://dx.doi.org/10.3892/ijmm.2017.3233 Text en Copyright: © Gu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Gu, Jian-Jun Fan, Kai-Chun Zhang, Jian-He Chen, Hong-Jie Wang, Shou-Sen Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling |
title | Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling |
title_full | Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling |
title_fullStr | Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling |
title_full_unstemmed | Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling |
title_short | Suppression of microRNA-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by PTEN/AKT signaling |
title_sort | suppression of microrna-130b inhibits glioma cell proliferation and invasion, and induces apoptosis by pten/akt signaling |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5746316/ https://www.ncbi.nlm.nih.gov/pubmed/29115407 http://dx.doi.org/10.3892/ijmm.2017.3233 |
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