General Information of the Ferroptosis Target (ID: TAR10062)
Target Name Voltage-dependent anion-selective channel protein 3 (VDAC3)
Synonyms
VDAC-3; hVDAC3; Outer mitochondrial membrane protein porin 3
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Gene Name VDAC3
Sequence
MCNTPTYCDLGKAAKDVFNKGYGFGMVKIDLKTKSCSGVEFSTSGHAYTDTGKASGNLET
KYKVCNYGLTFTQKWNTDNTLGTEISWENKLAEGLKLTLDTIFVPNTGKKSGKLKASYKR
DCFSVGSNVDIDFSGPTIYGWAVLAFEGWLAGYQMSFDTAKSKLSQNNFALGYKAADFQL
HTHVNDGTEFGGSIYQKVNEKIETSINLAWTAGSNNTRFGIAAKYMLDCRTSLSAKVNNA
SLIGLGYTQTLRPGVKLTLSALIDGKNFSAGGHKVGLGFELEA

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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
Q9Y277
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
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
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
Ref 1 The lncRNA BDNF-AS/WDR5/FBXW7 axis mediates ferroptosis in gastric cancer peritoneal metastasis by regulating VDAC3 ubiquitination. Int J Biol Sci. 2022 Jan 24;18(4):1415-1433. doi: 10.7150/ijbs.69454. eCollection 2022.
Ref 2 Nedd4 ubiquitylates VDAC2/3 to suppress erastin-induced ferroptosis in melanoma. Nat Commun. 2020 Jan 23;11(1):433. doi: 10.1038/s41467-020-14324-x.