General Information of the Disease (ID: DIS00007)
Name
Meningiomas
ICD
ICD-11: 2A01
Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Meningiomas [ICD-11: 2A01]
Responsed Regulator Junctional adhesion molecule C (JAM3) Suppressor
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell metastasis
In Vitro Model hMCCs (Human meningeal cells)
hPMCs (Human Primary Meningeal Cells)
hMCCs (Human meningeal cells)
IOMM-Lee cells Intracranial meningioma Homo sapiens CVCL_5779
CTCC-400-0154 (Human malignant meningioma cells)
In Vivo Model
Meningioma model mice were constructed as follows: after abdominal skin disinfection, 1% pentobarbital sodium (135 pL) was intraperitoneally injected into the nude mice. The head of the nude mice was fixed with a stereotaxometer, and two ear needles were symmetrically fixed in the bony parts slightly in front of each ear of the nude mice. The skin of the head of nude mice was cut approximately 0.6 cm lengthwise at 5 mm after the intersection of the inner canthal line and sagittal midline. The skin and fascia on both sides of the incision were bluntly separated with forceps to fully expose the skull. The location of the drill hole was determined according to the stereotactic anatomical map of the head: 0.5 mm behind the intersection of the coronal and sagittal suture and 2.5 mm to the right of the midline. The electric drill drilled a hole of approximately 1 mm at this position. The cells of the third generation of the logarithmic growth stage were taken. The cell suspension was absorbed with a 10 uL microsyringe, and the needle was slowly injected vertically to a depth of approximately 1.5 mm. The cell suspension (5 x 105 cells/100 uL) was slowly injected, and the needle remained for 2 min after injection before being slowly withdrawn.

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Response regulation miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells. Upregulation of miR-127-5p increased LDH, MDA, and ROS levels and Fe2+ content and inhibited the expression of GPX4 protein.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Meningiomas [ICD-11: 2A01]
Responsed Regulator hsa-miR-127-5p (miRNA) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell metastasis
In Vitro Model hMCCs (Human meningeal cells)
hPMCs (Human Primary Meningeal Cells)
hMCCs (Human meningeal cells)
IOMM-Lee cells Intracranial meningioma Homo sapiens CVCL_5779
CTCC-400-0154 (Human malignant meningioma cells)
In Vivo Model
Meningioma model mice were constructed as follows: after abdominal skin disinfection, 1% pentobarbital sodium (135 pL) was intraperitoneally injected into the nude mice. The head of the nude mice was fixed with a stereotaxometer, and two ear needles were symmetrically fixed in the bony parts slightly in front of each ear of the nude mice. The skin of the head of nude mice was cut approximately 0.6 cm lengthwise at 5 mm after the intersection of the inner canthal line and sagittal midline. The skin and fascia on both sides of the incision were bluntly separated with forceps to fully expose the skull. The location of the drill hole was determined according to the stereotactic anatomical map of the head: 0.5 mm behind the intersection of the coronal and sagittal suture and 2.5 mm to the right of the midline. The electric drill drilled a hole of approximately 1 mm at this position. The cells of the third generation of the logarithmic growth stage were taken. The cell suspension was absorbed with a 10 uL microsyringe, and the needle was slowly injected vertically to a depth of approximately 1.5 mm. The cell suspension (5 x 105 cells/100 uL) was slowly injected, and the needle remained for 2 min after injection before being slowly withdrawn.

    Click to Show/Hide
Response regulation miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells. Upregulation of miR-127-5p increased LDH, MDA, and ROS levels and Fe2+ content and inhibited the expression of GPX4 protein.
Unspecific Target
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Meningiomas [ICD-11: 2A01]
Responsed Regulator Myocyte-specific enhancer factor 2C (MEF2C) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CH-157MN cells Meningioma Homo sapiens CVCL_5723
IOMM-Lee cells Intracranial meningioma Homo sapiens CVCL_5779
PM3 (Human meningioma cells)
In Vivo Model
6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable.

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Response regulation MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low E-cadherin create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Meningiomas [ICD-11: 2A01]
Responsed Regulator Merlin (NF2) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CH-157MN cells Meningioma Homo sapiens CVCL_5723
IOMM-Lee cells Intracranial meningioma Homo sapiens CVCL_5779
PM3 (Human meningioma cells)
In Vivo Model
6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable.

    Click to Show/Hide
Response regulation MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low CDH1 (E-cadherin) create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Responsed Disease Meningiomas [ICD-11: 2A01]
Responsed Regulator Cadherin-1 (CDH1) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CH-157MN cells Meningioma Homo sapiens CVCL_5723
IOMM-Lee cells Intracranial meningioma Homo sapiens CVCL_5779
PM3 (Human meningioma cells)
In Vivo Model
6-week-old male nude mice (Nanjing Medical University Animal Center) were used in this study. There were 6-8 mice/group for survival and tumor growth analysis experiments. For tumor growth analysis, (2 x 106) IOMM-Lee-shMEF2C, IOMM-Lee-shMEF2C-Lv-NF2 or IOMM-Lee-shMEF2C-Lv-Ecad cells were subcutaneously injected to the right flank of the mice to examine the effect of MEF2C, NF2 and E-cadherin status on ferropotosis inducing response in vivo. Erastin, 15 mg/kg in 10% DMSO, or vehicle was administrated intraperitoneally (i.p.) every other day starting at Day 5 after implantation. Tumor diameter was recorded every 5 days starting at Day 10 when the tumors were visible and detectable.

    Click to Show/Hide
Response regulation MEF2C was found to drive the expression of both NF2 and E-cadherin. NF2 loss and low CDH1 (E-cadherin) create susceptibility to ferroptosis in meningioma. MEF2C could be a new molecular target in ferroptosis-inducing therapies for meningioma.
References
Ref 1 miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells. Dis Markers. 2022 Jul 2;2022:6423237. doi: 10.1155/2022/6423237. eCollection 2022.
Ref 2 MEF2C silencing downregulates NF2 and E-cadherin and enhances Erastin-induced ferroptosis in meningioma. Neuro Oncol. 2021 Dec 1;23(12):2014-2027. doi: 10.1093/neuonc/noab114.