Oncosuppressors and Oncogenes: Role in Haemangioma Genesis and Potential for Therapeutic Targeting

Mabeta, Peaceful Lucy

doi:10.3390/ijms19041192

Cited by 14 publications

(13 citation statements)

References 84 publications

(146 reference statements)

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“…Another possible mechanism leading to a lower level of VEGF is through the regulation of Bcl-2, a protein family composed of cell death regulators. It has been implicated in the differentiation of several cell types, including neuronal, epithelial and hematopoietic cells, as well as in the survival of endothelial cells ( 39 ). Karl et al described pro-angiogenic activity by Bcl-2 based on its ability to activate the NF-κB signaling pathway and elicit expression of the pro-angiogenic CXCL8 and CXCL1 chemokines in endothelial cells ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Mifepristone as a Potential Therapy to Reduce Angiogenesis and P-Glycoprotein Associated With Glioblastoma Resistance to Temozolomide

et al. 2020

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Glioblastoma, the most common primary central nervous system tumor, is characterized by extensive vascular neoformation and an area of necrosis generated by rapid proliferation. The standard treatment for this type of tumor is surgery followed by chemotherapy based on temozolomide and radiotherapy, resulting in poor patient survival. Glioblastoma is known for strong resistance to treatment, frequent recurrence and rapid progression. The aim of this study was to evaluate whether mifepristone, an antihormonal agent, can enhance the effect of temozolomide on C6 glioma cells orthotopically implanted in Wistar rats. The levels of the vascular endothelial growth factor (VEGF), and P-glycoprotein (P-gp) were examined, the former a promoter of angiogenesis that facilitates proliferation, and the latter an efflux pump transporter linked to drug resistance. After a 3-week treatment, the mifepristone/temozolomide regimen had decreased the level of VEGF and P-gp and significantly reduced tumor proliferation (detected by PET/CT images based on 18F-fluorothymidine uptake). Additionally, mifepristone proved to increase the intracerebral concentration of temozolomide. The lower level of O6-methylguanine-DNA-methyltransferase (MGMT) (related to DNA repair in tumors) previously reported for this combined treatment was herein confirmed. After the mifepristone/temozolomide treatment ended, however, the values of VEGF, P-gp, and MGMT increased and reached control levels by 14 weeks post-treatment. There was also tumor recurrence, as occurred when administering temozolomide alone. On the other hand, temozolomide led to 100% mortality within 26 days after beginning the drug treatment, while mifepristone/temozolomide enabled 70% survival 60–70 days and 30% survived over 100 days, suggesting that mifepristone could possibly act as a chemo-sensitizing agent for temozolomide.

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Section: Discussionmentioning

confidence: 99%

Mifepristone as a Potential Therapy to Reduce Angiogenesis and P-Glycoprotein Associated With Glioblastoma Resistance to Temozolomide

et al. 2020

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“…The abnormal activation of VEGFA and VEGFR2 on the cell surface endows robust capabilities of proliferation, colony formation, migration, and invasion ( 51 , 52 ). In addition, the activation of the VEGF signaling pathway may also be beneficial to the survival of hemangioma endothelial cells during angiogenesis and vasculogenesis ( 53 ). Besides, VEGF also acts in an autocrine manner to promote RAS activation and tumor cell growth through the VEGF receptor neuropilin-1 ( 54 ).…”

Section: Discussionmentioning

confidence: 99%

NOGOB receptor–mediated RAS signaling pathway is a target for suppressing proliferating hemangioma

Liu

Salato

et al. 2021

JCI Insight

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Infantile hemangioma is a vascular tumor characterized by the rapid growth of disorganized blood vessels followed by slow spontaneous involution. The underlying molecular mechanisms that regulate hemangioma proliferation and involution still are not well elucidated. Our previous studies reported that NOGOB receptor (NGBR), a transmembrane protein, is required for the translocation of prenylated RAS from the cytosol to the plasma membrane and promotes RAS activation. Here, we show that NGBR was highly expressed in the proliferating phase of infantile hemangioma, but its expression decreased in the involuting phase, suggesting that NGBR may have been involved in regulating the growth of proliferating hemangioma. Moreover, we demonstrate that NGBR knockdown in hemangioma stem cells (HemSCs) attenuated growth factor–stimulated RAS activation and diminished the migration and proliferation of HemSCs, which is consistent with the effects of RAS knockdown in HemSCs. In vivo differentiation assay further shows that NGBR knockdown inhibited blood vessel formation and adipocyte differentiation of HemSCs in immunodeficient mice. Our data suggest that NGBR served as a RAS modulator in controlling the growth and differentiation of HemSCs.

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“…In fact, there are differences in the expression of gene biomarkers in different stages of IH ( Ritter et al, 2002 ; Greenberger et al, 2010a ). P53 participated in the process of IH by regulating hypoxia-inducible factors and angiogenesis ( Mabeta, 2018 ). In addition, immune cells are involved in the development of IHs through mesenchymal transformation of endothelium ( Wu et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

Ouyang

et al. 2021

Front. Genet.

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BackgroundInfantile hemangioma (IH) is characterized by proliferation and regression.MethodsBased on the GSE127487 dataset, the differentially expressed genes (DEGs) between 6, 12, or 24 months and normal samples were screened, respectively. STEM software was used to screen the continued up-regulated or down-regulated in common genes. The modules were assessed by weighted gene co-expression network analysis (WGCNA). The enrichment analysis was performed to identified the biological function of important module genes. The area under curve (AUC) value and protein-protein interaction (PPI) network were used to identify hub genes. The differential expression of hub genes in IH and normal tissues was detected by qPCR.ResultsThere were 5,785, 4,712, and 2,149 DEGs between 6, 12, and 24 months and normal tissues. We found 1,218 DEGs were up-regulated or down-regulated expression simultaneously in common genes. They were identified as 10 co-expression modules. Module 3 and module 4 were positively or negatively correlated with the development of IH, respectively. These two module genes were significantly involved in immunity, cell cycle arrest and mTOR signaling pathway. The two module genes with AUC greater than 0.8 at different stages of IH were put into PPI network, and five genes with the highest degree were identified as hub genes. The differential expression of these genes was also verified by qRTPCR.ConclusionFive hub genes may distinguish for proliferative and regressive IH lesions. The WGCNA and PPI network analyses may help to clarify the molecular mechanism of IH at different stages.

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Oncosuppressors and Oncogenes: Role in Haemangioma Genesis and Potential for Therapeutic Targeting

Cited by 14 publications

References 84 publications

Mifepristone as a Potential Therapy to Reduce Angiogenesis and P-Glycoprotein Associated With Glioblastoma Resistance to Temozolomide

Mifepristone as a Potential Therapy to Reduce Angiogenesis and P-Glycoprotein Associated With Glioblastoma Resistance to Temozolomide

NOGOB receptor–mediated RAS signaling pathway is a target for suppressing proliferating hemangioma

Integrated WGCNA and PPI Network to Screen Hub Genes Signatures for Infantile Hemangioma

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