Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10455)
Regulator Name Aldo-keto reductase family 1 member C1 (AKR1C1)
Synonyms
DDH; DDH1; 20-alpha-hydroxysteroid dehydrogenase; Chlordecone reductase homolog HAKRC; Dihydrodiol dehydrogenase 1; High-affinity hepatic bile acid-binding protein
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Gene Name AKR1C1
Gene ID 1645
Regulator Type Protein coding
Uniprot ID Q04828
Sequence
MDSKYQCVKLNDGHFMPVLGFGTYAPAEVPKSKALEATKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWCNSHRPELVRPALERSLKNLQLDYVDLYLIHFPV
SVKPGEEVIPKDENGKILFDTVDLCATWEAVEKCKDAGLAKSIGVSNFNRRQLEMILNKP
GLKYKPVCNQVECHPYFNQRKLLDFCKSKDIVLVAYSALGSHREEPWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTSEEMKAIDGLN
RNVRYLTLDIFAGPPNYPFSDEY

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Family Aldo/keto reductase family
Function
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentrations of NADPH. Displays a broad positional specificity acting on positions 3, 17 and 20 of steroids and regulates the metabolism of hormones like estrogens and androgens. May also reduce conjugated steroids such as 5alpha- dihydrotestosterone sulfate. Displays affinity for bile acids.

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HGNC ID
HGNC:384
KEGG ID hsa:1645
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
AKR1C1 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
Unspecific Target [Unspecific Target]
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 cells Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
In Vivo Model
Mice in the + dox groups were fed a diet of doxycycline chow 3 days prior to injecting cells and throughout the remainder of the experiment. Mice in the -dox group were fed a diet of amoxicillin chow to avoid skin rash. Subcutaneous flank tumors were generated by injecting 5E6 A549 or 2E6 H460 confluent cells (n = 5 per group) suspended in 50% Matrigel into the right flank.

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Response regulation Concurrent loss-of-function mutations in STK11 and KEAP1 in lung adenocarcinoma (LUAD) are associated with aggressive tumor growth, resistance to available therapies, and early death. STK11/KEAP1 co-mutation results in significantly elevated expression of ferroptosis-protective genes, including SCD and AKR1C1/2/3, and resistance to pharmacologically induced ferroptosis.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
BEAS-2B cells Normal Homo sapiens CVCL_0168
Response regulation The expression of AKR1C1 was upregulated in non-small cell lung cancer (NSCLC) cell lines, and silencing AKR1C1 can inhibit the proliferation and migration of NSCLC cells and promote the occurrence of ferroptosis.
Experiment 3 Reporting the Ferroptosis Target of This Regulator [3]
Responsed Disease Dry eye disease ICD-11: 9A79
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCE-2 cells Normal Homo sapiens CVCL_3316
In Vivo Model
A total of 72 female C57BL/6J mice aged 6 to 8 weeks were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). The mice were injected subcutaneously with scopolamine hydrobromide (1.5 mg/0.3 mL; Sigma-Aldrich) three times daily for 5 consecutive days. Control mice matched for age and sex were maintained in an environment of 50% to 75% relative humidity.

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Response regulation Excessive oxidative stress-induced ferroptosis participates in dry eye disease (DED) pathogenesis. The expression of AKR1C1 is triggered by NRF2 to decrease ferroptosis-induced cell damage and inflammation in HCECs.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Aldo-keto reductase family 1 member C1 (AKR1C1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 NCI-H358 cells Minimally invasive lung adenocarcinoma Homo sapiens CVCL_1559
NCI-H292 cells Lung mucoepidermoid carcinoma Homo sapiens CVCL_0455
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H460 cells Lung large cell carcinoma Homo sapiens CVCL_0459
In Vivo Model
Mice in the + dox groups were fed a diet of doxycycline chow 3 days prior to injecting cells and throughout the remainder of the experiment. Mice in the -dox group were fed a diet of amoxicillin chow to avoid skin rash. Subcutaneous flank tumors were generated by injecting 5E6 A549 or 2E6 H460 confluent cells (n = 5 per group) suspended in 50% Matrigel into the right flank.

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Response regulation Concurrent loss-of-function mutations in STK11 and KEAP1 in lung adenocarcinoma (LUAD) are associated with aggressive tumor growth, resistance to available therapies, and early death. STK11/KEAP1 co-mutation results in significantly elevated expression of ferroptosis-protective genes, including SCD and AKR1C1/2/3, and resistance to pharmacologically induced ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Aldo-keto reductase family 1 member C1 (AKR1C1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
In Vitro Model
 A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
PC-9 cells Lung adenocarcinoma Homo sapiens CVCL_B260
NCI-H1975 cells Lung adenocarcinoma Homo sapiens CVCL_1511
BEAS-2B cells Normal Homo sapiens CVCL_0168
Response regulation The expression of AKR1C1 was upregulated in non-small cell lung cancer (NSCLC) cell lines, and silencing AKR1C1 can inhibit the proliferation and migration of NSCLC cells and promote the occurrence of ferroptosis.
Dry eye disease [ICD-11: 9A79]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [3]
Target Regulator Aldo-keto reductase family 1 member C1 (AKR1C1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HCE-2 cells Normal Homo sapiens CVCL_3316
In Vivo Model
A total of 72 female C57BL/6J mice aged 6 to 8 weeks were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). The mice were injected subcutaneously with scopolamine hydrobromide (1.5 mg/0.3 mL; Sigma-Aldrich) three times daily for 5 consecutive days. Control mice matched for age and sex were maintained in an environment of 50% to 75% relative humidity.

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Response regulation Excessive oxidative stress-induced ferroptosis participates in dry eye disease (DED) pathogenesis. The expression of AKR1C1 is triggered by NRF2 to decrease ferroptosis-induced cell damage and inflammation in HCECs.
References
Ref 1 Concurrent Mutations in STK11 and KEAP1 Promote Ferroptosis Protection and SCD1 Dependence in Lung Cancer. Cell Rep. 2020 Dec 1;33(9):108444. doi: 10.1016/j.celrep.2020.108444.
Ref 2 Ferroptosis-related gene AKR1C1 predicts the prognosis of non-small cell lung cancer. Cancer Cell Int. 2021 Oct 26;21(1):567. doi: 10.1186/s12935-021-02267-2.
Ref 3 AKR1C1 Protects Corneal Epithelial Cells Against Oxidative Stress-Mediated Ferroptosis in Dry Eye. Invest Ophthalmol Vis Sci. 2022 Sep 1;63(10):3. doi: 10.1167/iovs.63.10.3.