MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells

Background/Aims: Glial cell line-derived neurotrophic factor (GDNF) is an important factor promoting invasive glioma growth. This study was performed to reveal a unique mechanism of glioma cell proliferation and migration. Methods: Human U251 glioma cells were used to screen the optimal GDNF concent...

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Main Authors: Bao-Le Zhang, Fu-Lu Dong, Ting-Wen Guo, Xiao-He Gu, Lin-Yan Huang, Dian-Shuai Gao
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2017-12-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:https://www.karger.com/Article/FullText/485883
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author Bao-Le Zhang
Fu-Lu Dong
Ting-Wen Guo
Xiao-He Gu
Lin-Yan Huang
Dian-Shuai Gao
author_facet Bao-Le Zhang
Fu-Lu Dong
Ting-Wen Guo
Xiao-He Gu
Lin-Yan Huang
Dian-Shuai Gao
author_sort Bao-Le Zhang
collection DOAJ
description Background/Aims: Glial cell line-derived neurotrophic factor (GDNF) is an important factor promoting invasive glioma growth. This study was performed to reveal a unique mechanism of glioma cell proliferation and migration. Methods: Human U251 glioma cells were used to screen the optimal GDNF concentration and treatment time to stimulate proliferation and migration. MicroRNA (MiRNA) expression profiles were detected by microarray and confirmed by real-time polymerase chain reaction (PCR). The target genes of differentially expressed miRNAs were predicted by miRWalk, and those targeted by multiple miRNAs were screened with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A regulatory miRNA network was constructed using ingenuity pathway analysis (IPA). Target gene expression of differentially expressed miRNAs was examined by real-time PCR or mRNA microarray. Results: The results show that 50 ng/mL GDNF for 24 h significantly promotes U251 glioma cell proliferation and migration (P < 0.05). Seven miRNAs (hsa-miR-194-5p, hsa-miR-152-3p, hsa-miR-205-5p, hsa-miR-629-5p, hsa-miR-3609, hsa-miR-183-5p, and hsa-miR-487b-3p) were significantly up-regulated after GDNF treatment (P < 0.05). These miRNAs are primarily involved in signal transduction, cell adhesion and cell cycle through mitogen-activated protein kinase (MAPK) signaling, focal adhesion and glioma signal pathways. Five of these miRNAs (hsa-miR-194-5p, hsa-miR-152-3p, hsa-miR-205-5p, hsa-miR-183-5p, and hsa-miR-487b-3p) co-regulate TP53 and Akt. mRNA expression levels of four genes co-targeted by two or more up-regulated miRNAs were significantly decreased after GDNF treatment (P < 0.05). Conclusion: GDNF treatment of U251 glioma cells significantly increased the expression of seven miRNAs involved in cell adhesion and the cell cycle.
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spelling doaj.art-486590f914644b2b8398e47d61ee59742022-12-22T02:05:42ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782017-12-014451923193810.1159/000485883485883MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma CellsBao-Le ZhangFu-Lu DongTing-Wen GuoXiao-He GuLin-Yan HuangDian-Shuai GaoBackground/Aims: Glial cell line-derived neurotrophic factor (GDNF) is an important factor promoting invasive glioma growth. This study was performed to reveal a unique mechanism of glioma cell proliferation and migration. Methods: Human U251 glioma cells were used to screen the optimal GDNF concentration and treatment time to stimulate proliferation and migration. MicroRNA (MiRNA) expression profiles were detected by microarray and confirmed by real-time polymerase chain reaction (PCR). The target genes of differentially expressed miRNAs were predicted by miRWalk, and those targeted by multiple miRNAs were screened with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A regulatory miRNA network was constructed using ingenuity pathway analysis (IPA). Target gene expression of differentially expressed miRNAs was examined by real-time PCR or mRNA microarray. Results: The results show that 50 ng/mL GDNF for 24 h significantly promotes U251 glioma cell proliferation and migration (P < 0.05). Seven miRNAs (hsa-miR-194-5p, hsa-miR-152-3p, hsa-miR-205-5p, hsa-miR-629-5p, hsa-miR-3609, hsa-miR-183-5p, and hsa-miR-487b-3p) were significantly up-regulated after GDNF treatment (P < 0.05). These miRNAs are primarily involved in signal transduction, cell adhesion and cell cycle through mitogen-activated protein kinase (MAPK) signaling, focal adhesion and glioma signal pathways. Five of these miRNAs (hsa-miR-194-5p, hsa-miR-152-3p, hsa-miR-205-5p, hsa-miR-183-5p, and hsa-miR-487b-3p) co-regulate TP53 and Akt. mRNA expression levels of four genes co-targeted by two or more up-regulated miRNAs were significantly decreased after GDNF treatment (P < 0.05). Conclusion: GDNF treatment of U251 glioma cells significantly increased the expression of seven miRNAs involved in cell adhesion and the cell cycle.https://www.karger.com/Article/FullText/485883GliomaProliferation and migrationGDNFMiRNAMicroarray
spellingShingle Bao-Le Zhang
Fu-Lu Dong
Ting-Wen Guo
Xiao-He Gu
Lin-Yan Huang
Dian-Shuai Gao
MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells
Cellular Physiology and Biochemistry
Glioma
Proliferation and migration
GDNF
MiRNA
Microarray
title MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells
title_full MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells
title_fullStr MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells
title_full_unstemmed MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells
title_short MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells
title_sort mirnas mediate gdnf induced proliferation and migration of glioma cells
topic Glioma
Proliferation and migration
GDNF
MiRNA
Microarray
url https://www.karger.com/Article/FullText/485883
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