Systematic microRNA screening identifies miR-19b as regulator of temozolomide response through targeting PP2A serine-threonine phosphatase in glioblastoma
Kashani, E.; Hlavackova, K.; Haemmig, S.; Sadowski, M. C.; Phour, J.; Baumgartner, U.; Mueller-Wirth, N.; Trefny, C.; Sharf Den Abu Fakher, B.; Nydegger, C.; Maragkou, T.; Schucht, P.; Zinn, P.; Luedi, M.; Marti, T. M.; Krebs, P.; Vassella, E.
Show abstract
Despite the standard of care, glioblastoma IDH wildtype (GBM) inevitably recurs, underscoring the need to develop new treatment strategies. To address the role of microRNAs in temozolomide (TMZ) response, we performed functional microRNA screens and consistently identified miR-19b. Our study reveals a novel axis between miR-19b and PPP2R5E subunit of serine/threonine protein phosphatase PP2A and establishes a so far unappreciated contribution of miR-19b in TMZ resistance of GBM. Specifically, our results demonstrate that attenuation of miR-19b in GBM cell lines and glioblastoma stem cells (GSCs) induces DNA damage, which further enhances the cytotoxic effects of TMZ treatment. We confirmed TMZ resistance induced by knocking down PPP2R5E in orthotopic mouse xenografts of GSCs. Furthermore, our results indicate that treating cells with the PP2A-activating drug FTY720 or knocking down endogenous PP2A-inhibiting proteins potentiates the cytotoxic effects of TMZ. MiR-19b attenuation or PPP2R5E activation could potentially be exploited in adjuvant therapy of GBM patients.
Matching journals
The top 9 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Zinc Finger MYND-Type Containing 8 (ZMYND8) is epigenetically regulated in mutant Isocitrate Dehydrogenase 1 (IDH1) glioma to promote radioresistance 94%
- Preclinical modeling of surgery and steroid therapy for glioblastoma reveals changes in immunophenotype that are associated with tumor growth and outcome 94%
- Endoglin, a novel biomarker and therapeutical target to prevent malignant peripheral nerve sheath tumor growth and metastasis 94%
Similar papers in this journal
- Loss of EIF4G2 Mediates Aggressiveness in Distinct Human Endometrial Cancer Subpopulations with Poorer Survival Outcome in Patients 94%
- The long non-coding RNA SAMMSON is essential for uveal melanoma cell survival 94%
- Oncogenic RAS sensitizes cells to drug-induced replication stress via transcriptional silencing of P53 93%
Similar papers in this journal
- EMP3 sustains oncogenic EGFR/CDK2 signaling by restricting receptor degradation in glioblastoma 95%
- Capture at the single cell level of metabolic modules distinguishing aggressive and indolent glioblastoma cells 94%
- MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting Nuclear Factor I/B (NFIB) 94%
"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.