Ferroptosis Target Information
General Information of the Ferroptosis Target (ID: TAR10062)
Target Name | Voltage-dependent anion-selective channel protein 3 (VDAC3) | ||||
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Synonyms |
VDAC-3; hVDAC3; Outer mitochondrial membrane protein porin 3
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Gene Name | VDAC3 | ||||
Sequence |
MCNTPTYCDLGKAAKDVFNKGYGFGMVKIDLKTKSCSGVEFSTSGHAYTDTGKASGNLET
KYKVCNYGLTFTQKWNTDNTLGTEISWENKLAEGLKLTLDTIFVPNTGKKSGKLKASYKR DCFSVGSNVDIDFSGPTIYGWAVLAFEGWLAGYQMSFDTAKSKLSQNNFALGYKAADFQL HTHVNDGTEFGGSIYQKVNEKIETSINLAWTAGSNNTRFGIAAKYMLDCRTSLSAKVNNA SLIGLGYTQTLRPGVKLTLSALIDGKNFSAGGHKVGLGFELEA Click to Show/Hide
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Family | Eukaryotic mitochondrial porin family | ||||
Function |
Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules. Involved in male fertility and sperm mitochondrial sheath formation.
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Gene ID | 7419 | ||||
Uniprot ID | |||||
Target Type | Driver Suppressor Marker | ||||
Mechanism Diagram | Click to View the Original Diagram | ||||
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Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
VDAC3 can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
F-box/WD repeat-containing protein 7 (FBXW7)
Gastric cancer [ICD-11: 2B72]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator | [1] | ||||
Regulator for Ferroptosis | Driver | ||||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Four- to six-week-old nude mice (BALB/c) were purchased from Jiangsu Jicui Yaokang Biotechnology Co. Ltd. (Nanjing, China) and then randomly divided into 3 groups (n = 5 per group). PO-BDNF-AS-HGC-27 cells, PONC-BDNF-AS-HGC-27 cells, or PO-BDNF-AS + PO-FBXW7-HGC-27 cells (5 x 106) were suspended in 100 ul DMEM and subcutaneously injected into the flanks of the mice in each group. After 10 days, we measured the tumor size every week using digital Vernier calipers and calculated the tumor volume based on the formula: volume = 1/2 x (width2 x length). On the 30th day or when the tumor became larger than 1.5 cm in diameter, the mice were sacrificed. Subsequently, the subcutaneous graft tumors were removed for further experiments. For the intraabdominal tumor model, we randomly divided the mice into two groups (n = 6 per group). PO-BDNF-AS-HGC-27 cells or PONC-BDNF-AS-HGC-27 cells (8 x 106) were suspended in 150 uL DMEM and intraperitoneally injected into the mice in each group (weight, approximately 18.0-19.0 g). Five weeks after injection, the mice were euthanized and necropsied to assess abdominal tumor burden and tumor location. Finally, we detected the mRNA and protein expression levels of relevant genes in the tumor tissues by RT-PCR and western blotting assays.
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Response Description | BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in gastric cancer by affecting VDAC3 ubiquitination. | ||||
E3 ubiquitin-protein ligase NEDD4 (NEDD4)
Melanoma [ICD-11: 2C30]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator | [2] | ||||
Regulator for Ferroptosis | Suppressor | ||||
Pathway Response | Fatty acid metabolism | hsa01212 | |||
Ferroptosis | hsa04216 | ||||
Ubiquitin mediated proteolysis | hsa04120 | ||||
Cell Process | Cell ferroptosis | ||||
Cell proliferation | |||||
In Vitro Model |
A-375 cells | Amelanotic melanoma | Homo sapiens | CVCL_0132 | |
G-361 cells | Melanoma | Homo sapiens | CVCL_1220 | ||
MeWo cells | Melanoma | Homo sapiens | CVCL_0445 | ||
SK-MEL-2 cells (MEK inhibitor-resistant) cells | Melanoma | Homo sapiens | CVCL_0069 | ||
SK-MEL-3 cells | Cutaneous melanoma | Homo sapiens | CVCL_0550 | ||
SK-MEL-24 cells | Melanoma | Homo sapiens | CVCL_0599 | ||
WM2032 cells | Melanoma | Homo sapiens | CVCL_0B68 | ||
HEK-293T cells | Normal | Homo sapiens | CVCL_0063 | ||
In Vivo Model |
NU/NU Nude mice were purchased from Charles River (Beijing). To generate murine subcutaneous tumors, melanoma cells (5 x 106 cells per mouse) were injected subcutaneously into the left posterior flanks of 7-week-old immunodeficient female nude mice.
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Response Description | Knockdown of Nedd4 leads to elevated protein level of VDAC2/3, which increased the sensitivity of melanoma cells to erastin both in vitro and in vivo. | ||||
BDNF-AS (IncRNA)
Gastric cancer [ICD-11: 2B72]
In total 1 item(s) under this disease | |||||
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator | [1] | ||||
Regulator for Ferroptosis | Suppressor | ||||
Pathway Response | Ferroptosis | hsa04216 | |||
Cell Process | Cell ferroptosis | ||||
In Vitro Model |
AGS cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0139 | |
HGC-27 cells | Gastric carcinoma | Homo sapiens | CVCL_1279 | ||
BGC-823 cells | Gastric carcinoma | Homo sapiens | CVCL_3360 | ||
MGC-803 cells | Gastric mucinous adenocarcinoma | Homo sapiens | CVCL_5334 | ||
MKN45 cells | Gastric adenocarcinoma | Homo sapiens | CVCL_0434 | ||
GES-1 cells | Normal | Homo sapiens | CVCL_EQ22 | ||
In Vivo Model |
Four- to six-week-old nude mice (BALB/c) were purchased from Jiangsu Jicui Yaokang Biotechnology Co. Ltd. (Nanjing, China) and then randomly divided into 3 groups (n = 5 per group). PO-BDNF-AS-HGC-27 cells, PONC-BDNF-AS-HGC-27 cells, or PO-BDNF-AS + PO-FBXW7-HGC-27 cells (5 x 106) were suspended in 100 ul DMEM and subcutaneously injected into the flanks of the mice in each group. After 10 days, we measured the tumor size every week using digital Vernier calipers and calculated the tumor volume based on the formula: volume = 1/2 x (width2 x length). On the 30th day or when the tumor became larger than 1.5 cm in diameter, the mice were sacrificed. Subsequently, the subcutaneous graft tumors were removed for further experiments. For the intraabdominal tumor model, we randomly divided the mice into two groups (n = 6 per group). PO-BDNF-AS-HGC-27 cells or PONC-BDNF-AS-HGC-27 cells (8 x 106) were suspended in 150 uL DMEM and intraperitoneally injected into the mice in each group (weight, approximately 18.0-19.0 g). Five weeks after injection, the mice were euthanized and necropsied to assess abdominal tumor burden and tumor location. Finally, we detected the mRNA and protein expression levels of relevant genes in the tumor tissues by RT-PCR and western blotting assays.
Click to Show/Hide
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Response Description | BDNF-AS could regulate FBXW7 expression by recruiting WDR5, thus affecting FBXW7 transcription, and FBXW7 regulated the protein expression of VDAC3 through ubiquitination. Conclusively, our research demonstrated that the BDNF-AS/WDR5/FBXW7 axis regulates ferroptosis in gastric cancer by affecting VDAC3 ubiquitination. | ||||
References