MiRNAs Mediate GDNF-Induced Proliferation and Migration of Glioma Cells.

Abstract

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.

• Authors: Bao-Le Zhang, Fu-Lu Dong, Ting-Wen Guo, Xiao-He Gu, Lin-Yan Huang, Dian-Shuai Gao
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 44 Issue 5 Pg. 1923-1938 ( 2017) ISSN: 1421-9778 [Electronic] Germany
• PMID: 29224008 (Publication Type: Journal Article)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

• Glial Cell Line-Derived Neurotrophic Factor
• MicroRNAs
• TP53 protein, human
• Tumor Suppressor Protein p53
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases

Topics

• Cell Adhesion (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cluster Analysis
• Glial Cell Line-Derived Neurotrophic Factor (pharmacology)
• Glioma (metabolism, pathology)
• Humans
• MicroRNAs (genetics, metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Oligonucleotide Array Sequence Analysis
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Real-Time Polymerase Chain Reaction
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Up-Regulation (drug effects)