Upregulation of miR-181a suppresses the formation of glioblastoma stem cells by targeting the Notch2 oncogene and correlates with good prognosis in patients with glioblastoma multiforme

Huang, Shixiong; Zhao, Zhongyan; Weng, Guohu; He, Xiang-Ying; Wu, Chanji; Fu, Chuan‐Yi; Sui, Zhi-Yan; Ma, Yu‐Shui; Liu, Tao

doi:10.1016/j.bbrc.2017.04.008

Cited by 27 publications

(16 citation statements)

References 25 publications

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“…39,40 And miR-181a and miR-107 are also identified as important posttranscriptional regulators of Notch2 in glioma. 41,42 These findings not only contribute to understand the molecular mechanism of Notch1 and Notch2 dysregulation in glioma, but also provide possible targets for glioma intervention. Moreover, some other Notch1 or Notch2 inhibitors, such as γ-secretase inhibitors, are also clinically promising.…”

Section: Discussionmentioning

confidence: 85%

<p>Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis</p>

Wang

Hou

et al. 2020

CMAR

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Background: Glioma is one the most common and aggressive primary tumors of adult central nervous system worldwide, which tends to develop dysplasia and metastasis. Recently, toosendanin (TSN) has shown pharmacological effects in several cancers. However, little is known about the underlying mechanism of the effect of TSN on glioma and its relationship between miRNA in glioma. Methods: Cell proliferation, cell cycle, cell apoptosis and cell migration were analyzed by CCK-8 cell viability, flow cytometry, wound scratch healing, transwell and Western blotting assays, respectively, in vitro. The regulation relationships between TSN and miR-608 or between miR-608 and Notch1 (Notch2) were examined using qRT-PCR, dual-luciferase and Western blotting assays. The functional effects of TSN through regulating miR-608 and Notch1 (Notch2) were further examined using a xenograft tumor mouse model in vivo. Results: After TSN concentration was increased from 50 nM, 100 nM to 150 nM, cell proliferation and cell cycle were gradually reduced, and the cell apoptosis rate was increased in U-138MG or U-251MG cells. Wound-healing and transwell assays results showed that cell migration was significantly inhibited in TSN treatment cells (TSN treatment, 50 nM) compared to control cells. Mechanistic studies revealed that TSN up-regulated the expression of microRNA-608 (miR-608), while down-regulated the expression of miR-608's target, Notch1 and Notch2. Over-expression of Notch1 and Notch2 partly attenuated TSN-induced tumor suppressive function. Moreover, in vivo experiments revealed that TSN treatment led to a significant inhibition of tumor growth, suggesting that it might be a promising drug for the treatment of glioma. Conclusion: In the present study, a novel established functional manner of TSN/miR-608/ Notch1 (Notch2) axis was systematically indicated, which might provide prospective intervention ways for glioma therapy.

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Section: Discussionmentioning

confidence: 85%

<p>Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis</p>

Wang

Hou

et al. 2020

CMAR

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“…Tumor biomarkers in GBM 28389242 [62] Table 5. The biological functions, corresponding PubMed IDs and literatures for genes with large topological changes between NPC and astrocytes (Ast).…”

Section: Symbol: Gene Name Function Roles In Gbm Pmid Referencesmentioning

confidence: 99%

Kernel Differential Subgraph Analysis to Reveal the Key Period Affecting Glioblastoma

et al. 2020

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Glioblastoma (GBM) is a fast-growing type of malignant primary brain tumor. To explore the mechanisms in GBM, complex biological networks are used to reveal crucial changes among different biological states, which reflect on the development of living organisms. It is critical to discover the kernel differential subgraph (KDS) that leads to drastic changes. However, identifying the KDS is similar to the Steiner Tree problem that is an NP-hard problem. In this paper, we developed a criterion to explore the KDS (CKDS), which considered the connectivity and scale of KDS, the topological difference of nodes and function relevance between genes in the KDS. The CKDS algorithm was applied to simulated datasets and three single-cell RNA sequencing (scRNA-seq) datasets including GBM, fetal human cortical neurons (FHCN) and neural differentiation. Then we performed the network topology and functional enrichment analyses on the extracted KDSs. Compared with the state-of-art methods, the CKDS algorithm outperformed on simulated datasets to discover the KDSs. In the GBM and FHCN, seventeen genes (one biomarker, nine regulatory genes, one driver genes, six therapeutic targets) and KEGG pathways in KDSs were strongly supported by literature mining that they were highly interrelated with GBM. Moreover, focused on GBM, there were fifteen genes (including ten regulatory genes, three driver genes, one biomarkers, one therapeutic target) and KEGG pathways found in the KDS of neural differentiation process from activated neural stem cells (aNSC) to neural progenitor cells (NPC), while few genes and no pathway were found in the period from NPC to astrocytes (Ast). These experiments indicated that the process from aNSC to NPC is a key differentiation period affecting the development of GBM. Therefore, the CKDS algorithm provides a unique perspective in identifying cell-type-specific genes and KDSs.

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“…MiR-181a targets the 3′ UTR region of Notch2 in glioblastomas (57). The downregulation of Notch2 was reported to exert the same outcome as the downregulation of Notch1 (58).…”

Section: Normal Functions Of Ucmsc’s Extracellular Vesicles and Micromentioning

confidence: 99%

“…Notch2 was also suspected of participation in the EGFR/P13K/AKT pathway in conjunction with Notch1 (58). However, the exact mechanism of Notch-2 in gliomas is still debatable (57). The over-expression of Notch2 stimulates the malignancy of gliomas and GSC while the introduction of mir-181a successfully inhibits them (57).…”

Section: Normal Functions Of Ucmsc’s Extracellular Vesicles and Micromentioning

confidence: 99%

“…However, the exact mechanism of Notch-2 in gliomas is still debatable (57). The over-expression of Notch2 stimulates the malignancy of gliomas and GSC while the introduction of mir-181a successfully inhibits them (57). Another study confirmed miR-181a as a potential glioblastoma treatment by sensitising the glioblastomas to radiation through B-cell lymphoma 2 protein (Bcl-2) downregulation, an anti-apoptotic protein (59, 60).…”

Section: Normal Functions Of Ucmsc’s Extracellular Vesicles and Micromentioning

confidence: 99%

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Advancing towards Effective Glioma Therapy: MicroRNA Derived from Umbilical Cord Mesenchymal Stem Cells’ Extracellular Vesicles

Ngadiono

Hardiany

2019

MJMS

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A glioma, especially a grade IV glioblastoma, is a malignant tumour with a poor prognosis despite growing medical advancements. Researchers have been looking for better and more effective treatments targeting the molecular pathways of gliomas due to glioblastomas’ ability to develop resistance to chemotherapies. Moreover, glioma stem cells (GSC) contribute to maintaining the glioma population, which benefits from its ability to self-renew and differentiate. Recent research has reported that through the introduction of umbilical cord mesenchymal stem cells (UCMSC) into glioma cells, the growth and development of the glioma cells can be downregulated. It has more currently been found out that UCMSC release extracellular vesicles (EVs) containing miRNA that are responsible for this phenomenon. Therefore, this review analyses literature to discuss all possible miRNAs contained within the UCMSC’s EVs and to elaborate on their molecular mechanisms in halting gliomas and GSC growth. This review will also include the challenges and limitations, to account for which more in vivo research is suggested. In conclusion, this review highlights how miRNAs contained within UCMSC’s EVs are able to downregulate multiple prominent pathways in the survival of gliomas.

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Upregulation of miR-181a suppresses the formation of glioblastoma stem cells by targeting the Notch2 oncogene and correlates with good prognosis in patients with glioblastoma multiforme

Cited by 27 publications

References 25 publications

<p>Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis</p>

<p>Toosendanin Suppresses Glioma Progression Property and Induces Apoptosis by Regulating miR-608/Notch Axis</p>

Kernel Differential Subgraph Analysis to Reveal the Key Period Affecting Glioblastoma

Advancing towards Effective Glioma Therapy: MicroRNA Derived from Umbilical Cord Mesenchymal Stem Cells’ Extracellular Vesicles

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