Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10164)
Regulator Name Transcription factor SOX-2 (SOX2)
Gene Name SOX2
Gene ID 6657
Regulator Type Protein coding
Uniprot ID P48431
Sequence
MYNMMETELKPPGPQQTSGGGGGNSTAAAAGGNQKNSPDRVKRPMNAFMVWSRGQRRKMA
QENPKMHNSEISKRLGAEWKLLSETEKRPFIDEAKRLRALHMKEHPDYKYRPRRKTKTLM
KKDKYTLPGGLLAPGGNSMASGVGVGAGLGAGVNQRMDSYAHMNGWSNGSYSMMQDQLGY
PQHPGLNAHGAAQMQPMHRYDVSALQYNSMTSSQTYMNGSPTYSMSYSQQGTPGMALGSM
GSVVKSEASSSPPVVTSSSHSRAPCQAGDLRDMISMYLPGAEVPEPAAPSRLHMSQHYQS
GPVPGTAINGTLPLSHM

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Function
Transcription factor that forms a trimeric complex with OCT4 on DNA and controls the expression of a number of genes involved in embryonic development such as YES1, FGF4, UTF1 and ZFP206. Binds to the proximal enhancer region of NANOG. Critical for early embryogenesis and for embryonic stem cell pluripotency. Downstream SRRT target that mediates the promotion of neural stem cell self-renewal. Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation. May function as a switch in neuronal development.

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HGNC ID
HGNC:11195
KEGG ID hsa:6657
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
SOX2 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]
 Target Info 
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hTCs (Human tumour cells)
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
HEK-293T cells Normal Homo sapiens CVCL_0063
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
In Vivo Model
Mice were housed in the SIBCB animal facility under SPF conditions with a 12 hours light/dark cycle at room temperature. For Erastin treatment, we sequentially dissolved Erastin in 5% DMSO, 30% PEG300, 5% Tween80 and ddH2O according to the manufacturers instructions, it should be noted that the solvent needed to be added from left to right, after the dissolution was completely clear, added the next reagent, 40 mg/kg Erastin was intraperitoneal injected, every other day for 2 weeks. For IKE treatment, 50 mg/kg IKE was intraperitoneal injected, once a day for 2 weeks.

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Response regulation Tumors with high SOX2 expression were more resistant to ferroptosis, and SLC7A11 expression was positively correlated with SOX2 in both mouse and human lung cancer tissue. This study uncovers a SOX2-SLC7A11 regulatory axis that confers resistance to ferroptosis in lung cancer stem-like cells.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Target for Ferroptosis Suppressor
Responsed Disease Chronic kidney disease ICD-11: GB61
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 mKTs (Mouse knee tissues)
HK-2 (Human renal glomerular endothelial cells)
In Vivo Model
All C57BL/6 mice (5-6 weeks, 18-20 g) were obtained from Animal Testing Center of Qinglongshan (Nanjing, Suzhou, China). DN mice were fed with a high-fat diet (HFD) for 12 weeks and then injected with STZ (30 mg/kg of streptozotocin; Sigma-Aldrich, St Louis, MO, USA) i.p. for 7 consecutive days. Blood glucose levels of mice were measured using 16.7 mmol/l after one week of the final injection. Then, mice were killed under anesthesia and their kidneys taken for analysis after induction of STZ at 4 months.

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Response regulation Circular RNA circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/ SLC7A11 by miR-770-5p. Importantly, this research indicated that circ ASAP2 might act as a target for improving the role of ferroptosis in diabetes nephropathy.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Transcription factor SOX-2 (SOX2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 hTCs (Human tumour cells)
NCI-H1299 cells Lung large cell carcinoma Homo sapiens CVCL_0060
SW620 cells Colon adenocarcinoma Homo sapiens CVCL_0547
HEK-293T cells Normal Homo sapiens CVCL_0063
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
In Vivo Model
Mice were housed in the SIBCB animal facility under SPF conditions with a 12 hours light/dark cycle at room temperature. For Erastin treatment, we sequentially dissolved Erastin in 5% DMSO, 30% PEG300, 5% Tween80 and ddH2O according to the manufacturers instructions, it should be noted that the solvent needed to be added from left to right, after the dissolution was completely clear, added the next reagent, 40 mg/kg Erastin was intraperitoneal injected, every other day for 2 weeks. For IKE treatment, 50 mg/kg IKE was intraperitoneal injected, once a day for 2 weeks.

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Response regulation Tumors with high SOX2 expression were more resistant to ferroptosis, and SLC7A11 expression was positively correlated with SOX2 in both mouse and human lung cancer tissue. This study uncovers a SOX2-SLC7A11 regulatory axis that confers resistance to ferroptosis in lung cancer stem-like cells.
Chronic kidney disease [ICD-11: GB61]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Transcription factor SOX-2 (SOX2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 mKTs (Mouse knee tissues)
HK-2 (Human renal glomerular endothelial cells)
In Vivo Model
All C57BL/6 mice (5-6 weeks, 18-20 g) were obtained from Animal Testing Center of Qinglongshan (Nanjing, Suzhou, China). DN mice were fed with a high-fat diet (HFD) for 12 weeks and then injected with STZ (30 mg/kg of streptozotocin; Sigma-Aldrich, St Louis, MO, USA) i.p. for 7 consecutive days. Blood glucose levels of mice were measured using 16.7 mmol/l after one week of the final injection. Then, mice were killed under anesthesia and their kidneys taken for analysis after induction of STZ at 4 months.

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Response regulation Circular RNA circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/ SLC7A11 by miR-770-5p. Importantly, this research indicated that circ ASAP2 might act as a target for improving the role of ferroptosis in diabetes nephropathy.
References
Ref 1 Stem Cell Factor SOX2 Confers Ferroptosis Resistance in Lung Cancer via Upregulation of SLC7A11. Cancer Res. 2021 Oct 15;81(20):5217-5229. doi: 10.1158/0008-5472.CAN-21-0567. Epub 2021 Aug 12.
Ref 2 Circ ASAP2 decreased inflammation and ferroptosis in diabetic nephropathy through SOX2/SLC7A11 by miR-770-5p. Acta Diabetol. 2023 Jan;60(1):29-42. doi: 10.1007/s00592-022-01961-5. Epub 2022 Sep 24.