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Status |
Public on Nov 05, 2020 |
Title |
Targeting the HuR oncogenic role with a new class of inhibitors of HuR dimerization |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Comprehensive meta-analysis and target screening confirmed that the mRNA-binding protein of ELAV-family HuR is oncogenic and universally upregulated in brain tumors, which highlight HuR as an universal chemotherapeutic target. HuR functionality in cancer cells is strictly dependent on HuR nuclear/cytoplasmic shuttling and dimerization; therefore, we developed a new class of inhibitors of HuR protein dimerization by utilizing medicinal chemistry techniques and reporter cell-based assay of HuR dimerization. The therapeutic potentials of lead compound (SRI-42127) were evaluated in five primary patient-derived glioma xenolines of classic, proneural, and mesenchymal subtypes, in vitro, and in mouse glioma model, in vivo. The Illumina global RNA-Sequencing was performed on PDGx-derived glioma neurospheres of different subtypes after treatment with DMSO (control) or SRI-42127 (3 uM) for 12 h to analysis transcripts and cell-signaling pathways affected by new inhibitor of HuR dimerization.
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Overall design |
Two biological replicates were analyzed for each of five PDGx cell lines in two different conditions: i) afte treatment with inhibitor of HuR dimerization SRI-42127, 3 uM for 12 hours; ii) after treatment with corresponding DMSO concentration for 12 hours.
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Contributor(s) |
Yang X, Filippova N, Crossman DK, Nabors LB |
Citation(s) |
33096700 |
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Submission date |
Sep 21, 2020 |
Last update date |
Nov 05, 2020 |
Contact name |
Louis Burt Nabors |
E-mail(s) |
bnabors@uab.edu
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Phone |
2059341432
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Organization name |
University of Alabama at Birmingham
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Department |
Neurology
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Lab |
Neuro-oncology Lab
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Street address |
510 20th Street South, FOT 1020
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City |
Birmingham |
State/province |
AL |
ZIP/Postal code |
35294 |
Country |
USA |
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Platforms (1) |
GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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Samples (20)
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Relations |
BioProject |
PRJNA664706 |
SRA |
SRP284223 |