Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10472)
Regulator Name Aldo-keto reductase family 1 member C3 (AKR1C3)
Synonyms
17-beta-hydroxysteroid dehydrogenase type 5; 3-alpha-HSD type II, brain; 3-alpha-hydroxysteroid dehydrogenase type 2; Chlordecone reductase homolog HAKRb; Dihydrodiol dehydrogenase 3; Dihydrodiol dehydrogenase type I; HA1753; Prostaglandin F synthase; Testosterone 17-beta-dehydrogenase 5
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Gene Name AKR1C3
Gene ID 8644
Regulator Type Protein coding
Uniprot ID P42330
Sequence
MDSKHQCVKLNDGHFMPVLGFGTYAPPEVPRSKALEVTKLAIEAGFRHIDSAHLYNNEEQ
VGLAIRSKIADGSVKREDIFYTSKLWSTFHRPELVRPALENSLKKAQLDYVDLYLIHSPM
SLKPGEELSPTDENGKVIFDIVDLCTTWEAMEKCKDAGLAKSIGVSNFNRRQLEMILNKP
GLKYKPVCNQVECHPYFNRSKLLDFCKSKDIVLVAYSALGSQRDKRWVDPNSPVLLEDPV
LCALAKKHKRTPALIALRYQLQRGVVVLAKSYNEQRIRQNVQVFEFQLTAEDMKAIDGLD
RNLHYFNSDSFASHPNYPYSDEY

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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. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone. Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH. Acts preferentially as a 17- ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone. Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol. Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol). Also displays retinaldehyde reductase activity toward 9-cis-retinal.

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HGNC ID
HGNC:386
KEGG ID hsa:8644
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
AKR1C3 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 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Suppressor
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
Cell metastasis
In Vitro Model
 Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
HEK-293T cells Normal Homo sapiens CVCL_0063
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
MHCC97-H cells Adult hepatocellular carcinoma Homo sapiens CVCL_4972
HCC-LY10 (Human hepatoma cells)
In Vivo Model
To generate murine subcutaneous tumors, 2 x 106 HCC cells were injected subcutaneously to the right of the dorsal midline in nude mice. Once the tumors reached approximately 100 mm3 at day 15, mice were randomly allocated into groups and treated with erastin or sorafenib for 2 weeks.

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Response regulation Overexpression of AKR1C3 protected against ferroptosis in hepatocellular carcinoma (HCC) cells. Mechanistically, AKR1C3 regulated ferroptosis through YAP/SLC7A11 signaling in HCC.
Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Response regulation AKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in hepatocellular carcinoma (HCC). AKR1C3 inhibitors may be used in conjunction with sorafenib to become a better therapeutic target for HCC.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [3]
Responsed Disease Acute myocardial infarction ICD-11: BA41
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
Response regulation AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of acute myocardial infarction (AMI).
Hepatocellular carcinoma [ICD-11: 2C12]
 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 C3 (AKR1C3) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Hippo signaling pathway hsa04390
Cell Process Cell ferroptosis
Cell proliferation
Cell metastasis
In Vitro Model
 Hep 3B2.1-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0326
HEK-293T cells Normal Homo sapiens CVCL_0063
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
MHCC97-H cells Adult hepatocellular carcinoma Homo sapiens CVCL_4972
HCC-LY10 (Human hepatoma cells)
In Vivo Model
To generate murine subcutaneous tumors, 2 x 106 HCC cells were injected subcutaneously to the right of the dorsal midline in nude mice. Once the tumors reached approximately 100 mm3 at day 15, mice were randomly allocated into groups and treated with erastin or sorafenib for 2 weeks.

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Response regulation Overexpression of AKR1C3 protected against ferroptosis in hepatocellular carcinoma (HCC) cells. Mechanistically, AKR1C3 regulated ferroptosis through YAP/SLC7A11 signaling in HCC.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Aldo-keto reductase family 1 member C3 (AKR1C3) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
PI3K-Akt signaling pathway hsa04151
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Response regulation AKR1C3 can induce sorafenib resistance through promoting the phosphorylation of AKT in hepatocellular carcinoma (HCC). AKR1C3 inhibitors may be used in conjunction with sorafenib to become a better therapeutic target for HCC.
Acute myocardial infarction [ICD-11: BA41]
 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 C3 (AKR1C3) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 HEK-293T cells Normal Homo sapiens CVCL_0063
CHO-S/H9C2 cells Normal Cricetulus griseus CVCL_A0TS
Response regulation AKR1C3 and HOXB4 are promising diagnostic biomarkers, providing novel insights into the ferroptosis mechanisms of acute myocardial infarction (AMI).
References
Ref 1 AKR1C3 suppresses ferroptosis in hepatocellular carcinoma through regulation of YAP/SLC7A11 signaling pathway. Mol Carcinog. 2023 Jun;62(6):833-844. doi: 10.1002/mc.23527. Epub 2023 Mar 15.
Ref 2 Knockdown of AKR1C3 Promoted Sorafenib Sensitivity Through Inhibiting the Phosphorylation of AKT in Hepatocellular Carcinoma. Front Oncol. 2022 Mar 11;12:823491. doi: 10.3389/fonc.2022.823491. eCollection 2022.
Ref 3 AKR1C3 and Its Transcription Factor HOXB4 Are Promising Diagnostic Biomarkers for Acute Myocardial Infarction. Front Cardiovasc Med. 2021 Sep 9;8:694238. doi: 10.3389/fcvm.2021.694238. eCollection 2021.