Molecular mechanism of Notch signaling with special emphasis on microRNAs: Implications for glioma

Du, Ying; Chen, Hao; Li, Xiaofeng; Lu, Yujiao; Feng, Yongzeng; Zhang, Lei

doi:10.1002/jcp.26775

Cited by 30 publications

(26 citation statements)

References 127 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As an important mediator of cancer-related signaling, Notch signaling was an evolutionarily conserved and demonstrated to be associated with glioma. 38 Our data in this study showed that over-expression of Notch1 and Notch2 could promote glioma cell proliferation and migration, which was inhibited by TSNincreased miR-608. Therefore, Notch1 and Notch2 stand out as particular targets for glioma prevention.…”

Section: Discussionmentioning

confidence: 58%

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

Wang

Hou

et al. 2020

CMAR

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 58%

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

Wang

Hou

et al. 2020

CMAR

View full text Add to dashboard Cite

show abstract

“…NOTCH1. 29 hES, 30 Cyclin D1 31 and MMP2 32 were proved to promote Notch signaling pathway activation, while p21, 33 cleaved caspase-3, 34 cleaved PARP 35 and E-cadherin 36 were reported to interdict it. To verify our prediction, the expression of these above proteins that related to Notch signaling pathway, in U138 and U251 cells that after transfection were detected using Western blot.…”

Section: Discussionmentioning

confidence: 99%

NR5A2 Promotes Cell Growth and Resistance to Temozolomide Through Regulating Notch Signal Pathway in Glioma

Yang¹,

Deng²,

Li³

et al. 2020

OTT

View full text Add to dashboard Cite

Background: Glioma is a fatal primary malignant tumor. We aimed to explore the effect of nuclear receptor subfamily 5 group A member 2 (NR5A2) on glioma. Methods: NR5A2 expression in glioma tissues and cells was detected using qRT-PCR and immunohistochemistry (IHC)/Western blot. SPSS 22.0 was performed to explore the relationship between NR5A2 expression and glioma clinicopathologic features. The downexpressed plasmid of NR5A2 was transfected into glioma cells, and the cell viability, proliferation, apoptosis, migration, and invasion were respectively determined by MTT, EdU, flow cytometry, wound healing and transwell assays. Cell cycle was analyzed using flow cytometry. Temozolomide (TMZ)-resistant glioma cells were established to define the effect of NR5A2 on drug resistance. The expressions of Notch pathway-related proteins were assessed by Western blot. Glioma nude mice model was constructed to explore the role of NR5A2 played in vivo. Results: NR5A2 was highly expressed in glioma tissues and cell lines. NR5A2 overexpression was related to the poor prognosis of glioma patients. NR5A2 knockdown inhibited cell viability, proliferation, migration, and invasion, induced cell cycle arrest and promoted cell apoptosis in U138 and U251 cells. In U138/TMZ and U251/TMZ cell lines, NR5A2 upregulation enhanced TMZ resistance while NR5A2 downregulation reduced it. The knockdown of NR5A2 influenced the expressions of Notch pathway-related proteins. NR5A2 knockdown suppressed tumor growth and facilitated apoptosis in glioma mice model. Conclusion: NR5A2 affected glioma cell malignant behaviors and TMZ resistance via Notch signaling pathway and it might be a novel target in glioma therapy.

show abstract

“… 4 , 5 , 6 , However, differential expression of certain miRNAs might be also involved in pathophysiological mechanisms of GBM recurrence, but there are limited data regarding miRNA expression as GBM progresses (at its recurrence). 7 , 8 , Comprehensive knowledge and understanding of the molecular pathways underlying disease progression, tumor recurrence and response to therapy might be of great importance in future development of more efficient therapies in GBM.…”

Section: Introductionmentioning

confidence: 99%

Dynamic expression of 11 miRNAs in 83 consecutive primary and corresponding recurrent glioblastoma: correlation to treatment, time to recurrence, overall survival and MGMT methylation status

Matos

Boštjančič

Matjašič

et al. 2018

Radiology and Oncology

View full text Add to dashboard Cite

BackgroundGlioblastoma (GBM) is the most common and the most malignant glioma subtype. Among numerous genetic alterations, miRNAs contribute to pathogenesis of GBM and it is suggested that also to GBM recurrence and resistance to therapy. Based on publications, we have selected 11 miRNAs and analyzed their expression in GBM. We hypothesized that selected miRNAs are differentially expressed and involved in primary as well as in recurrent GBM, that show significant expressional differences when different treatment options are in question, and that are related to certain patients and tumor characteristics.Patients and methodsParaffin embedded tissues, obtained from primary and corresponding recurrent tumor from 83 patients with primary GBM were used. Eleven miRNAs (miR-7, miR-9, miR-15b, miR-21, miR-26b, miR-124a, miR-199a, let-7a, let-7b, let-7d, and let-7f) were selected for qPCR expression analysis. For patients who received temozolamide (TMZ) as chemotherapeutic drug, O6-methylguanine-DNA methyltransferase (MGMT) methylation status was defined using the methyl-specific PCR.ResultsThere was a significant change in expression of miR-7, miR-9, miR-21, miR-26b, mirR-124a, miR-199a and let-7f in recurrent tumor compared to the primary. In recurrent tumor, miR-15b, let-7d and let-7f significantly changed comparing both treatment options. We also observed difference in progression free survival between patients that received radiotherapy and patients that received radiotherapy and chemotherapy, and longer survival for patients who received chemotherapy after second surgery compared to not treated patients. miR-26b showed correlation to progression free survival and let-7f to overall survival. We did not find any expression difference between the tumors with and without methylated MGMT.ConclusionsOur data suggest that analyzed miRNAs may not only contribute to pathogenesis of primary GBM, but also to tumor progression and its recurrence. Moreover, expression of certain miRNAs appears to be therapy-dependent and as such they might serve as additional biomarker for recurrence prediction and potentially predict a therapy-resistance.

show abstract

Molecular mechanism of Notch signaling with special emphasis on microRNAs: Implications for glioma

Cited by 30 publications

References 127 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>

<p><em>NR5A2</em> Promotes Cell Growth and Resistance to Temozolomide Through Regulating Notch Signal Pathway in Glioma</p>

Dynamic expression of 11 miRNAs in 83 consecutive primary and corresponding recurrent glioblastoma: correlation to treatment, time to recurrence, overall survival and MGMT methylation status

Contact Info

Product

Resources

About