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MicroRNA 145 enhances chemosensitivity of glioblastoma stem cells to demethoxycurcumin

Authors Qian C, Wang B, Zou Y, Zhang Y, Hu X, Sun W, Xiao H, Liu H, Shi L

Received 26 March 2019

Accepted for publication 30 May 2019

Published 24 July 2019 Volume 2019:11 Pages 6829—6840

DOI https://doi.org/10.2147/CMAR.S210076

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Melinda Thomas

Peer reviewer comments 3

Editor who approved publication: Dr Kenan Onel


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 Shi2

1Department 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 work

Background: 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


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