MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin
Chunfa Qian,*,1 Bin Wang,*,2 Yuanjie Zou,*,1 Yansong Zhang,*,1 Xinhua Hu,*,1 Wenbo Sun,*,1 Hong Xiao,*,3 Hongyi Liu,1 Lei Shi21Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, P...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-07-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/microrna-145-enhances-chemosensitivity-of-glioblastoma-stem-cells-to-d-peer-reviewed-article-CMAR |
| _version_ | 1818478757663473664 |
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| author | Qian C Wang B Zou Y Zhang Y Hu X Sun W Xiao H Liu H Shi L |
| author_facet | Qian C Wang B Zou Y Zhang Y Hu X Sun W Xiao H Liu H Shi L |
| author_sort | Qian C |
| collection | DOAJ |
| description | Chunfa Qian,*,1 Bin Wang,*,2 Yuanjie Zou,*,1 Yansong Zhang,*,1 Xinhua Hu,*,1 Wenbo Sun,*,1 Hong Xiao,*,3 Hongyi Liu,1 Lei Shi21Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Suzhou 215300, People’s Republic of China; 3Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workBackground: The presence of glioma stem cells (GSCs) is thought to be a key factor responsible for development of the incurable glioblastoma multiforme (GBM). GSCs are often displayed during chemotherapy resistance, except for demethoxycurcumin (DMC), a component of curcumin, which has been previously confirmed to inhibit GSCs proliferation and induce apoptosis.Purpose: The objective of this study was to identify the main mechanism underlying anti-GSCs resistance by DMC.Patients and methods: qRT-PCR was used to determine the expression of miR-145 in glioma patients and GSCs, and GSCs were transfected with miR-145 overexpressed vectors. Then, functional analyses (in vitro and in vivo) were performed to confirm the role of miR-145 and DMC in GSCs. Finally, related proteins were tested by immunohistochemistry and Western blot.Results: miR-145 was atypically low-expressed miRNA in GSCs, and could enhance GSC chemosensitivity to DMC both in vitro and in vivo. Upregulation of miR-145 in GSCs resulted in increased cell growth inhibition and apoptosis to DMC. Further research on the mechanism demonstrated that the combined effects of miR-145 and DMC were involved in the miR-145/SOX2-Wnt/β-catenin pathway. Overexpression of SOX2 reduced GSC resistance to growth inhibition by miR-145+ DMC treatment.Conclusion: Our data strongly support an important role for miR-145 in enhancing GSC chemosensitivity to DMC by targeting the SOX2-Wnt/β-catenin axis.Keywords: glioma stem cells, miR-145, demethoxycurcumin, proliferation, apoptosis |
| first_indexed | 2024-12-10T09:52:03Z |
| format | Article |
| id | doaj.art-17e767538c3f4313908fd342ca101ce2 |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-10T09:52:03Z |
| publishDate | 2019-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-17e767538c3f4313908fd342ca101ce22022-12-22T01:53:37ZengDove Medical PressCancer Management and Research1179-13222019-07-01Volume 116829684047353MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcuminQian CWang BZou YZhang YHu XSun WXiao HLiu HShi LChunfa Qian,*,1 Bin Wang,*,2 Yuanjie Zou,*,1 Yansong Zhang,*,1 Xinhua Hu,*,1 Wenbo Sun,*,1 Hong Xiao,*,3 Hongyi Liu,1 Lei Shi21Department of Neurosurgery, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People’s Republic of China; 2Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Suzhou 215300, People’s Republic of China; 3Department of Neuro-Psychiatric Institute, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210029, People’s Republic of China*These authors contributed equally to this workBackground: The presence of glioma stem cells (GSCs) is thought to be a key factor responsible for development of the incurable glioblastoma multiforme (GBM). GSCs are often displayed during chemotherapy resistance, except for demethoxycurcumin (DMC), a component of curcumin, which has been previously confirmed to inhibit GSCs proliferation and induce apoptosis.Purpose: The objective of this study was to identify the main mechanism underlying anti-GSCs resistance by DMC.Patients and methods: qRT-PCR was used to determine the expression of miR-145 in glioma patients and GSCs, and GSCs were transfected with miR-145 overexpressed vectors. Then, functional analyses (in vitro and in vivo) were performed to confirm the role of miR-145 and DMC in GSCs. Finally, related proteins were tested by immunohistochemistry and Western blot.Results: miR-145 was atypically low-expressed miRNA in GSCs, and could enhance GSC chemosensitivity to DMC both in vitro and in vivo. Upregulation of miR-145 in GSCs resulted in increased cell growth inhibition and apoptosis to DMC. Further research on the mechanism demonstrated that the combined effects of miR-145 and DMC were involved in the miR-145/SOX2-Wnt/β-catenin pathway. Overexpression of SOX2 reduced GSC resistance to growth inhibition by miR-145+ DMC treatment.Conclusion: Our data strongly support an important role for miR-145 in enhancing GSC chemosensitivity to DMC by targeting the SOX2-Wnt/β-catenin axis.Keywords: glioma stem cells, miR-145, demethoxycurcumin, proliferation, apoptosishttps://www.dovepress.com/microrna-145-enhances-chemosensitivity-of-glioblastoma-stem-cells-to-d-peer-reviewed-article-CMARglioma stem cellsmiR-145demethoxycurcuminproliferationapoptosis |
| spellingShingle | Qian C Wang B Zou Y Zhang Y Hu X Sun W Xiao H Liu H Shi L MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin Cancer Management and Research glioma stem cells miR-145 demethoxycurcumin proliferation apoptosis |
| title | MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin |
| title_full | MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin |
| title_fullStr | MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin |
| title_full_unstemmed | MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin |
| title_short | MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin |
| title_sort | microrna 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin |
| topic | glioma stem cells miR-145 demethoxycurcumin proliferation apoptosis |
| url | https://www.dovepress.com/microrna-145-enhances-chemosensitivity-of-glioblastoma-stem-cells-to-d-peer-reviewed-article-CMAR |
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