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Series GSE134190 Query DataSets for GSE134190
Status Public on Sep 14, 2019
Title Regulation of stem cell property and drug resistance of cancer cells by targeting transcriptional machinery via inhibition of neddylation
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary MLN4924, also known as pevonedistat, is a small molecule inhibitor of NEDD8 activating enzyme (NAE), that inhibits the entire neddylation pathway. As the first-in-class neddylation inhibitor, MLN4924 is currently in Phase I/II clinical trials for anticancer application as a single agent or in combination with chemotherapeutic drugs. MLN4924 has shown impressive anticancer activity by inactivating Cullin-RING ligases (CRLs) to cause accumulation of tumor suppressor substrates. Whether MLN4924 regulates the RNA expression by modulating the levels of transcription factor/repressor remain elusive. In this study, we treated A549 lung cancer cells with MLN4924 at 0.25 or 0.5 µM for 8 or 24 hrs, respectively, followed by RNAseq analysis. Here we found that MLN4924 significantly decreases the SOX2 mRNA level. The mechanistic study revealed that MLN4924 inhibits FBXW2 E3 to cause MSX2 accumulation, which in turn transcriptionally represses SOX2, leading to suppression of stem cell property and sensitization of cancer cells to tamoxifen.
Overall design Transcriptome analysis was performed in A549 cells after MLN4924 treatment for 8 or 24 hrs (6 groups, n=2 per group).
Contributor(s) Xie C, Sun Y
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Submission date Jul 12, 2019
Last update date Sep 15, 2019
Contact name Chuanming Xie
Organization name University of Michigan
Department Department of Radiation Oncology
Street address 4424B MS-1, 1301 Catherine Street
City Ann Arbor
State/province MI
ZIP/Postal code 48109
Country USA
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (12)
GSM3938584 A549 cells, MLN 0µM 8h Replicate 1
GSM3938585 A549 cells, MLN 0.25µM 8h Replicate 1
GSM3938586 A549 cells, MLN 0.5µM 8h Replicate 1
BioProject PRJNA554253
SRA SRP214431

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Supplementary file Size Download File type/resource
GSE134190_Differential_expression_genes.xlsx 97.5 Kb (ftp)(http) XLSX
GSE134190_gene_sample_count_with_symbol.txt.gz 1.5 Mb (ftp)(http) TXT
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