General Information of the Disease (ID: DIS00024)
Name
Oral squamous cell carcinoma
ICD
ICD-11: 2B6E
Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Tongue squamous cell carcinoma [ICD-11: 2B6E]
Responsed Drug Quisinostat Investigative
Responsed Regulator Cellular tumor antigen p53 (TP53) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Apoptosis hsa04210
Necroptosis hsa04217
Cell Process Cell ferroptosis
Cell proliferation
Cell apoptosis
Cell pyroptosis
In Vitro Model CAL-27 cells Tongue adenosquamous carcinom Homo sapiens CVCL_1107
Tca8113 cells Endocervical adenocarcinoma Homo sapiens CVCL_6851
In Vivo Model
Adult male athymic BALB/c nude mice (20-22 g of 5-week-old mice) were housed in a controlled environment at 23 ± 2 and 40%-70% humidity under a 12 h dark/light cycle with free access to irradiated food and sterile water. A suspension of 6 x 106/100 uL TCA-8113 cells was inoculated subcutaneously into the hind flank region of each nude mouse. The average tumor volume in nude mice reached 100 mm3, and mice were randomly divided into three groups. Quisinostat was formulated in normal saline and administered at 3 and 10 mg/kg/day byintraperitoneal injection. Control mice were given equal volume saline intraperitoneally. The tumor volume and the bodyweight of mice were monitored every three days.

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Response regulation Quisinostat could increase the apoptosis rate in the tumor tissues of nude mice. Up-regulation of the expression of p53 and down-regulated expression of GPX4 in cell lines were observed by immunofluorescent staining, and the expression locations of p53 and GPX4 proteins in TSCC cells were observed. Quisinostat may be a potential drug for the treatment of tongue squamous cell carcinoma.
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Responsed Drug Carnosic acid Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Response regulation The current findings highlight that carnosic acid may re-sensitize cisplatin-resistant cells to cisplatin by inducing ferroptosis, which involves the inactivation of Nrf2/HO-1/xCT pathway. Hence, this research may support a promising therapeutic approach to overcome chemoresistance in Oral squamous cell carcinoma.
Heme oxygenase 1 (HMOX1)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Responsed Drug Carnosic acid Investigative
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Response regulation The current findings highlight that carnosic acid may re-sensitize cisplatin-resistant cells to cisplatin by inducing ferroptosis, which involves the inactivation of Nrf2/HO-1/xCT pathway. Hence, this research may support a promising therapeutic approach to overcome chemoresistance in Oral squamous cell carcinoma.
Cystine/glutamate transporter (SLC7A11)
In total 5 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Suppressor
Responsed Disease Tongue squamous cell carcinoma [ICD-11: 2B6E]
Responsed Regulator Histone-lysine N-methyltransferase EZH2 (EZH2) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model Tca8113 cells Endocervical adenocarcinoma Homo sapiens CVCL_6851
TSCCA cells Endocervical adenocarcinoma Homo sapiens CVCL_VL15
CAL-27 cells Tongue adenosquamous carcinom Homo sapiens CVCL_1107
SCC-9 cells Tongue squamous cell carcinoma Homo sapiens CVCL_1685
hTECs (Human tongue epithelial cells)
Response regulation EZH2 inhibits the ferroptosis of tongue squamous cell carcinoma cells by inhibiting miR-125b-5p and enhancing SLC7A11. MiR-125b-5p regulates ferroptosis in TSCC cells by targeting SLC7A11.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Target for Ferroptosis Suppressor
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Responsed Regulator hsa-miR-34c-3p (miRNA) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model SCC-25 cells Squamous carcinoma Homo sapiens CVCL_1682
CAL-27 cells Tongue adenosquamous carcinom Homo sapiens CVCL_1107
HOK cells Normal Hexagrammos otakii CVCL_YE19
Response regulation Low expression of miR-34c-3p in oral squamous cell carcinoma, negatively regulating SLC7A11 expression, promoting ferroptosis, and suppressing cell proliferation.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Suppressor
Responsed Disease Tongue squamous cell carcinoma [ICD-11: 2B6E]
Responsed Regulator hsa-miR-125b-5p (miRNA) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model Tca8113 cells Endocervical adenocarcinoma Homo sapiens CVCL_6851
TSCCA cells Endocervical adenocarcinoma Homo sapiens CVCL_VL15
CAL-27 cells Tongue adenosquamous carcinom Homo sapiens CVCL_1107
SCC-9 cells Tongue squamous cell carcinoma Homo sapiens CVCL_1685
hTECs (Human tongue epithelial cells)
Response regulation EZH2 inhibits the ferroptosis of tongue squamous cell carcinoma cells by inhibiting miR-125b-5p and enhancing SLC7A11. MiR-125b-5p regulates ferroptosis in TSCC cells by targeting SLC7A11.
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Target for Ferroptosis Suppressor
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Responsed Regulator hsa-miR-520d-5p (miRNA) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CAL-27 cells Tongue adenosquamous carcinom Homo sapiens CVCL_1107
SCC-15 cells Tongue squamous cell carcinoma Homo sapiens CVCL_1681
In Vivo Model
The tumorigenicity analysis was conducted in BALB/c nude mice (6-weeks-old, male). The mice were maintained at pathogen-free condition. The 5 x 106 CAL27 cells were treated with control shRNA or circFNDC3B shRNA and subcutaneously injected into the nude mice (N = 5). The mice were sacrificed after 30 days and the tumor volume was calculated using the formula of (length x width2)/2.

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Response regulation CircFNDC3B attenuated ferroptosis of Oral squamous cell carcinoma (OSCC) cells and contributed to OSCC progression by regulating the miR-520d-5p/SLC7A11 axis. CircFNDC3B, miR-520d-5p, and SLC7A11 may serve as potential therapeutic targets of OSCC.
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Target for Ferroptosis Suppressor
Responsed Disease Oral squamous cell carcinoma [ICD-11: 2B6E.0]
Responsed Regulator CircFNDC3B (circRNA) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model CAL-27 cells Tongue adenosquamous carcinom Homo sapiens CVCL_1107
SCC-15 cells Tongue squamous cell carcinoma Homo sapiens CVCL_1681
In Vivo Model
The tumorigenicity analysis was conducted in BALB/c nude mice (6-weeks-old, male). The mice were maintained at pathogen-free condition. The 5 x 106 CAL27 cells were treated with control shRNA or circFNDC3B shRNA and subcutaneously injected into the nude mice (N = 5). The mice were sacrificed after 30 days and the tumor volume was calculated using the formula of (length x width2)/2.

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Response regulation CircFNDC3B attenuated ferroptosis of Oral squamous cell carcinoma (OSCC) cells and contributed to OSCC progression by regulating the miR-520d-5p/SLC7A11 axis. CircFNDC3B, miR-520d-5p, and SLC7A11 may serve as potential therapeutic targets of OSCC.
References
Ref 1 Death by histone deacetylase inhibitor quisinostat in tongue squamous cell carcinoma via apoptosis, pyroptosis, and ferroptosis. Toxicol Appl Pharmacol. 2021 Jan 1;410:115363. doi: 10.1016/j.taap.2020.115363. Epub 2020 Dec 5.
Ref 2 Induction of ferroptosis by carnosic acid-mediated inactivation of Nrf2/HO-1 potentiates cisplatin responsiveness in OSCC cells. Mol Cell Probes. 2022 Aug;64:101821. doi: 10.1016/j.mcp.2022.101821. Epub 2022 Apr 29.
Ref 3 EZH2-mediated SLC7A11 upregulation via miR-125b-5p represses ferroptosis of TSCC. Oral Dis. 2023 Apr;29(3):880-891. doi: 10.1111/odi.14040. Epub 2021 Nov 15.
Ref 4 MiR-34c-3p upregulates erastin-induced ferroptosis to inhibit proliferation in oral squamous cell carcinomas by targeting SLC7A11. Pathol Res Pract. 2022 Mar;231:153778. doi: 10.1016/j.prp.2022.153778. Epub 2022 Jan 25.
Ref 5 Circular RNA FNDC3BProtects Oral Squamous Cell Carcinoma Cells From Ferroptosis and Contributes to the Malignant Progression by Regulating miR-520d-5p/SLC7A11 Axis. Front Oncol. 2021 Aug 9;11:672724. doi: 10.3389/fonc.2021.672724. eCollection 2021.