CRISPR-Cas9 Screen Reveals PSMB3 Contributes to Gliomagenesis Through Proteasome-Dependent and Independent Mechanisms
Baisiwala, S.; Budhiraja, S.; Zolp, A.; Nandoliya, K.; Chen, L.; Park, C.; Perrault, E.; Saathoff, M.; Dmello, C.; Shireman, J.; Lin, P.; Dara, G.; McCortney, K.; Horbinski, C.; Sonabend, A.; Ahmed, A. U.
Show abstract
Glioblastoma (GBM) is the most common adult malignant brain tumor, with a median survival of 21 months and a 100% recurrence rate. Even though many of the critical oncogenic drivers for GBM have been identified, the basis of gliomagenesis is still under investigation. To identify novel genes that contribute to GBM progression, we performed a genome-wide CRISPR-Cas9 knockout screen. We identified four previously unstudied genes - PSMB3, CHCHD4, SPDYE5, HSPA1 - which had elevated expression in cancer and demonstrated a significant positive correlation with respect to GBM growth and patient survival in vivo and patient datasets. Furthermore, overexpression of PSMB3 and HSPA5 in neural stem cells resulted in transformation to a cancer phenotype. Further investigation of PSMB3, a subunit of the proteasome, allowed us to identify both ubiquitin-mediated and non-ubiquitin-mediated mechanisms of oncogenesis. Ultimately, the data from our CRISPR screens suggests that these genes drive tumor progression, making them promising therapeutic targets for GBM.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- EMP3 sustains oncogenic EGFR/CDK2 signaling by restricting receptor degradation in glioblastoma 96%
- Cellular Reprogramming of H3K27M Pediatric High-Grade Glioma to Neuron-like State 95%
- Capture at the single cell level of metabolic modules distinguishing aggressive and indolent glioblastoma cells 95%
Similar papers in this journal
Similar papers in this journal
- Human RAP2A Homolog of the Drosophila Asymmetric Cell Division Regulator Rap2l Targets the Stemness of Glioblastoma Stem Cells 96%
- Metabolic reprogramming of cancer cells by JMJD6-mediated pre-mRNA splicing is associated with therapeutic response to splicing inhibitor 95%
- Genetic Screen Identified Prmt5 as a Neuroprotection Target against Cerebral Ischemia 95%
Similar papers in this journal
- THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression 99%
- Subclonal evolution and expansion of THY1-positive cells is associated with recurrence in glioblastoma 96%
- Probing the glioma micro-environment: analysis using biopsy in combination with ultra-fast cyclic immunolabeling 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.