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Knockdown of RAD18 inhibits glioblastoma development
Author(s) -
Xie Chen,
Lu Dejuan,
Xu Meng,
Qu Zhengyi,
Zhang Weiguang,
Wang Hongwei
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28713
Subject(s) - gene knockdown , transfection , pdgfra , small interfering rna , microbiology and biotechnology , biology , viability assay , downregulation and upregulation , chemistry , cancer research , apoptosis , cell culture , gene , biochemistry , genetics , gist , stromal cell
This study aimed at investigating the role of RAD18 in the regulation of glioblastoma development as well as the underlying mechanisms. The human glioblastoma U251 and U87MG cells were transfected with siRNAs specifically targeting RAD18, and the effects of knockdown of RAD18 on the viability, apoptosis, migration, and invasion of U251 and U87MG cells were investigated. Transcriptome sequencing of the siRNA‐RAD18‐tranfected and siRNA‐NC‐transfected U251 cells was performed, followed by bioinformatic analyses for sequencing data. The results showed that knockdown of RAD18 significantly inhibited cell viability, promoted apoptosis, and suppressed migration and invasion of U251 and U87MG cells. Bioinformatic analyses of sequencing data identified 1,051 differentially expressed genes (DEGs) (369 up‐ and 682 downregulated genes) in the siRNA‐RAD18‐transfected U251 cells compared with siRNA‐NC‐transfected U251 cells. Eleven DEGs, including nerve growth factor (NGF), colony‐stimulating factor 2 (CSF2), matrix metallopeptidase 1 (MMP1), platelet‐derived growth factor receptor α (PDGFRA), and heme oxygenase 1 (HMOX1), were identified as the hub nodes in protein–protein interaction (PPI) network. Moreover, the aforementioned 11 hub genes were significantly enriched in PI3K–Akt signaling pathway and GO functions associated with the extracellular region. Notably, quantitative real‐time polymerase chain reaction further confirmed that the expression levels of NGF, CSF2, HMOX1, and MMP1 were significantly downregulated, while that of PDGFRA was markedly upregulated in the siRNA‐RAD18‐transfected U251 cells than in the siRNA‐NC cells. In conclusion, the knockdown of RAD18 may inhibit glioblastoma development by regulating the expression of the aforementioned key DEGs.