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Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis
Glioma is the most common and malignant form of primary brain tumour, and is characterised by high proliferation and extensive invasion and neurological destruction. Demethylzeylasteral (T-96), which is extracted from Tripterygium wilfordii, is considered to have immunosuppressive, anti-inflammatory...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180101/ https://www.ncbi.nlm.nih.gov/pubmed/30305611 http://dx.doi.org/10.1038/s41419-018-1086-8 |
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author | Zhang, Kui Fu, Gang Pan, Guangzhao Li, Chongyang Shen, Li Hu, Renjian Zhu, Shunqin Chen, Yibiao Cui, Hongjuan |
author_facet | Zhang, Kui Fu, Gang Pan, Guangzhao Li, Chongyang Shen, Li Hu, Renjian Zhu, Shunqin Chen, Yibiao Cui, Hongjuan |
author_sort | Zhang, Kui |
collection | PubMed |
description | Glioma is the most common and malignant form of primary brain tumour, and is characterised by high proliferation and extensive invasion and neurological destruction. Demethylzeylasteral (T-96), which is extracted from Tripterygium wilfordii, is considered to have immunosuppressive, anti-inflammatory and anti-angiogenic effects. Here, the anti-tumour effect of T-96 on glioma was evaluated. Our results demonstrated that T-96 significantly inhibited glioma cell growth and induced cell cycle arrest in G1 phase but did not induce apoptosis. Cell invasion and migration were dramatically suppressed after treatment with T-96. Almost all genes related to cell cycle and DNA replication were downregulated after treatment with T-96. Our results showed that miR-30e-5p was noticeably upregulated after T-96 treatment, and MYBL2, which is involved in cell cycle progression and is a target gene of miR-30e-5p, was significantly reduced in synchrony. Overexpression of MYBL2 partially rescued the T-96-induced inhibition of cell growth and proliferation. Moreover, a miR-30e-5p antagomir significantly reduced the upregulation of miR-30e-5p expression induced by T-96, leading to recovery of MYBL2 expression, and partially rescued the T-96-induced inhibition of cell growth and proliferation. More important, T-96 effectively upregulated miR-30e-5p expression and downregulated MYBL2 expression, thus inhibiting LN-229 cell tumour growth in a mouse model. These results indicated that T-96 might inhibit glioma cell growth by regulating the miR-30e-5p/MYBL2 axis. Our study demonstrated that T-96 might act as a promising agent for malignant glioma therapy. |
format | Online Article Text |
id | pubmed-6180101 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61801012018-10-11 Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis Zhang, Kui Fu, Gang Pan, Guangzhao Li, Chongyang Shen, Li Hu, Renjian Zhu, Shunqin Chen, Yibiao Cui, Hongjuan Cell Death Dis Article Glioma is the most common and malignant form of primary brain tumour, and is characterised by high proliferation and extensive invasion and neurological destruction. Demethylzeylasteral (T-96), which is extracted from Tripterygium wilfordii, is considered to have immunosuppressive, anti-inflammatory and anti-angiogenic effects. Here, the anti-tumour effect of T-96 on glioma was evaluated. Our results demonstrated that T-96 significantly inhibited glioma cell growth and induced cell cycle arrest in G1 phase but did not induce apoptosis. Cell invasion and migration were dramatically suppressed after treatment with T-96. Almost all genes related to cell cycle and DNA replication were downregulated after treatment with T-96. Our results showed that miR-30e-5p was noticeably upregulated after T-96 treatment, and MYBL2, which is involved in cell cycle progression and is a target gene of miR-30e-5p, was significantly reduced in synchrony. Overexpression of MYBL2 partially rescued the T-96-induced inhibition of cell growth and proliferation. Moreover, a miR-30e-5p antagomir significantly reduced the upregulation of miR-30e-5p expression induced by T-96, leading to recovery of MYBL2 expression, and partially rescued the T-96-induced inhibition of cell growth and proliferation. More important, T-96 effectively upregulated miR-30e-5p expression and downregulated MYBL2 expression, thus inhibiting LN-229 cell tumour growth in a mouse model. These results indicated that T-96 might inhibit glioma cell growth by regulating the miR-30e-5p/MYBL2 axis. Our study demonstrated that T-96 might act as a promising agent for malignant glioma therapy. Nature Publishing Group UK 2018-10-10 /pmc/articles/PMC6180101/ /pubmed/30305611 http://dx.doi.org/10.1038/s41419-018-1086-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhang, Kui Fu, Gang Pan, Guangzhao Li, Chongyang Shen, Li Hu, Renjian Zhu, Shunqin Chen, Yibiao Cui, Hongjuan Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis |
title | Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis |
title_full | Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis |
title_fullStr | Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis |
title_full_unstemmed | Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis |
title_short | Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis |
title_sort | demethylzeylasteral inhibits glioma growth by regulating the mir-30e-5p/mybl2 axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180101/ https://www.ncbi.nlm.nih.gov/pubmed/30305611 http://dx.doi.org/10.1038/s41419-018-1086-8 |
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