ArticleCancer medicine2015
Downregulation of RND3/RhoE in glioblastoma patients promotes tumorigenesis through augmentation of notch transcriptional complex activity.
Article in Cancer medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 25 citations in OpenAlex.
- Review
- Rnd3 regulates lung cancer cell invasion and migration independently of ROCK1 signaling via alpha 5 integrin modulation.Life science alliance · 2026Article
- Nano-Based Technology in Glioblastoma.Molecules (Basel, Switzerland) · 2025Review
- Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.Biomolecules · 2024Review
- RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages.Journal of immunology research · 2024Article
- Transcriptomic patterns in early-secretory and mid-secretory endometrium in a natural menstrual cycle immediately before in vitro fertilization and embryo transfer.Obstetrics & gynecology science · 2023Article
- Article
- Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating the PPARγ-UCP2 cascade.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Notch intracellular domain regulates glioblastoma proliferation through the Notch1 signaling pathway.Oncology letters · 2021Article
- Elevated RBP-Jκ and CXCL11 Expression in Colon Cancer is Associated with an Unfavorable Clinical Outcome.Cancer management and research · 2021Article
- Identification and characterization of a new isoform of small GTPase RhoE.Communications biology · 2020Article
- Ingenuity pathway analysis of differentially expressed genes involved in signaling pathways and molecular networks in RhoE gene‑edited cardiomyocytes.International journal of molecular medicine · 2020Article
- RND2 attenuates apoptosis and autophagy in glioblastoma cells by targeting the p38 MAPK signalling pathway.Journal of experimental & clinical cancer research : CR · 2020Article
- Small GTPase RHOE/RND3, a new critical regulator of NF-κB signalling in glioblastoma multiforme?Cell proliferation · 2019Article
- Biliverdin administration regulates the microRNA-mRNA expressional network associated with neuroprotection in cerebral ischemia reperfusion injury in rats.International journal of molecular medicine · 2019Article
- RhoE Fine-Tunes Inflammatory Response in Myocardial Infarction.Circulation · 2019Article
- Long Non-Coding RNA HOXA-AS2 Enhances The Malignant Biological Behaviors In Glioma By Epigenetically Regulating RND3 Expression.OncoTargets and therapy · 2019Article
- Review: Synthetic scaffolds to control the biochemical, mechanical, and geometrical environment of stem cell-derived brain organoids.APL bioengineering · 2018Review
- Retracted Article: MiR-182-5p and miR-96-5p increased hepatocellular carcinoma cell mobility, proliferation and cisplatin resistance partially by targeting RND3.RSC advances · 2018Article
- Genetic deletion ofOncotarget · 2017Article
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
Abstract
Activation of Notch signaling contributes to glioblastoma multiform (GBM) tumorigenesis. However, the molecular mechanism that promotes the Notch signaling augmentation during GBM genesis remains largely unknown. Identification of new factors that regulate Notch signaling is critical for tumor treatment. The expression levels of RND3 and its clinical implication were analyzed in GBM patients. Identification of RND3 as a novel factor in GBM genesis was demonstrated in vitro by cell experiments and in vivo by a GBM xenograft model. We found that RND3 expression was significantly decreased in human glioblastoma. The levels of RND3 expression were inversely correlated with Notch activity, tumor size, and tumor cell proliferation, and positively correlated with patient survival time. We demonstrated that RND3 functioned as an endogenous repressor of the Notch transcriptional complex. RND3 physically interacted with NICD, CSL, and MAML1, the Notch transcriptional complex factors, promoted NICD ubiquitination, and facilitated the degradation of these cofactor proteins. We further revealed that RND3 facilitated the binding of NICD to FBW7, a ubiquitin ligase, and consequently enhanced NICD protein degradation. Therefore, Notch transcriptional activity was inhibited. Forced expression of RND3 repressed Notch signaling, which led to the inhibition of glioblastoma cell proliferation in vitro and tumor growth in the xenograft mice in vivo. Downregulation of RND3, however, enhanced Notch signaling activity, and subsequently promoted glioma cell proliferation. Inhibition of Notch activity abolished RND3 deficiency-mediated GBM cell proliferation. We conclude that downregulation of RND3 is responsible for the enhancement of Notch activity that promotes glioblastoma genesis.
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