Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10233)
Regulator Name 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial (DECR1)
Synonyms
DECR, SDR18C1; 2,4-dienoyl-CoA reductase [NADPH]; Short chain dehydrogenase/reductase family 18C member 1
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Gene Name DECR1
Gene ID 1666
Regulator Type Protein coding
Uniprot ID Q16698
Sequence
MKLPARVFFTLGSRLPCGLAPRRFFSYGTKILYQNTEALQSKFFSPLQKAMLPPNSFQGK
VAFITGGGTGLGKGMTTLLSSLGAQCVIASRKMDVLKATAEQISSQTGNKVHAIQCDVRD
PDMVQNTVSELIKVAGHPNIVINNAAGNFISPTERLSPNAWKTITDIVLNGTAFVTLEIG
KQLIKAQKGAAFLSITTIYAETGSGFVVPSASAKAGVEAMSKSLAAEWGKYGMRFNVIQP
GPIKTKGAFSRLDPTGTFEKEMIGRIPCGRLGTVEELANLAAFLCSDYASWINGAVIKFD
GGEEVLISGEFNDLRKVTKEQWDTIEELIRKTKGS

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Family Short-chain dehydrogenases/reductases (SDR) family
Function
Auxiliary enzyme of beta-oxidation. It participates in the metabolism of unsaturated fatty enoyl-CoA esters having double bonds in both even- and odd-numbered positions in mitochondria. Catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to yield trans-3-enoyl-CoA.

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HGNC ID
HGNC:2753
KEGG ID hsa:1666
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
DECR1 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 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Prostate cancer ICD-11: 2C82
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Citrate cycle hsa00020
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 PNT1 cells Normal Homo sapiens CVCL_4804
PNT2 cells Normal Homo sapiens CVCL_2164
LNCaP cells Prostate carcinoma Homo sapiens CVCL_0395
VCaP cells Prostate carcinoma Homo sapiens CVCL_2235
22Rv1 cells Prostate carcinoma Homo sapiens CVCL_1045
MR49F cells Prostate carcinoma Homo sapiens CVCL_RW53
In Vivo Model
LNCaP cells (5 x 106 cells in 50 uL 10% FBS/RPMI 1640 medium) were co-injected subcutaneously with 50 uL Matrigel in 6-week-old NOD Scid Gamma male mice (Bioresource Facility, Austin Health, Heidelberg, Australia). When tumors reached~200 mm3, mice were randomized in different therapy groups.

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Response regulation DECR1 knockdown selectively inhibited -oxidation of PUFAs, inhibited proliferation and migration of prostate cancer cells, including treatment resistant lines, and suppressed tumor cell proliferation and metastasis in mouse xenograft models.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Prostate cancer ICD-11: 2C82
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 LNCaP cells Prostate carcinoma Homo sapiens CVCL_0395
LNCaP C4-2 cells Prostate carcinoma Homo sapiens CVCL_4782
CWR22 cells Prostate carcinoma Homo sapiens CVCL_3967
In Vivo Model
20 x 106 cells/mouse were suspended in serum-free medium and mixed with Matrigel (Corning, NY, USA) in a 1:1 ratio. 50 ul of cell suspension were injected orthotopically into the anterior prostate lobe of CD1-nude mice (Charles River Laboratories, Wilmington, MA, USA). Orchidectomy was performed at the time of injection. Tumours were allowed to grow for ~6 weeks after injection and tumour growth was monitored weekly using a Vevo3100 ultrasound imaging system (Fujifilm Visualsonics, The Netherlands).

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Response regulation DECR1 participates in redox homeostasis by controlling the balance between saturated and unsaturated phospholipids. DECR1 knockout induces ER stress and sensitises castration-resistant prostate cancer (CRPC) cells to ferroptosis.
Prostate cancer [ICD-11: 2C82]
 Disease Info 
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial (DECR1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Citrate cycle hsa00020
Cell Process Cell ferroptosis
Cell proliferation
Cell migration
Cell invasion
In Vitro Model
 PNT1 cells Normal Homo sapiens CVCL_4804
PNT2 cells Normal Homo sapiens CVCL_2164
LNCaP cells Prostate carcinoma Homo sapiens CVCL_0395
VCaP cells Prostate carcinoma Homo sapiens CVCL_2235
22Rv1 cells Prostate carcinoma Homo sapiens CVCL_1045
MR49F cells Prostate carcinoma Homo sapiens CVCL_RW53
In Vivo Model
LNCaP cells (5 x 106 cells in 50 uL 10% FBS/RPMI 1640 medium) were co-injected subcutaneously with 50 uL Matrigel in 6-week-old NOD Scid Gamma male mice (Bioresource Facility, Austin Health, Heidelberg, Australia). When tumors reached~200 mm3, mice were randomized in different therapy groups.

    Click to Show/Hide
Response regulation DECR1 knockdown selectively inhibited -oxidation of PUFAs, inhibited proliferation and migration of prostate cancer cells, including treatment resistant lines, and suppressed tumor cell proliferation and metastasis in mouse xenograft models.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator 2,4-dienoyl-CoA reductase [(3E)-enoyl-CoA-producing], mitochondrial (DECR1) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 LNCaP cells Prostate carcinoma Homo sapiens CVCL_0395
LNCaP C4-2 cells Prostate carcinoma Homo sapiens CVCL_4782
CWR22 cells Prostate carcinoma Homo sapiens CVCL_3967
In Vivo Model
20 x 106 cells/mouse were suspended in serum-free medium and mixed with Matrigel (Corning, NY, USA) in a 1:1 ratio. 50 ul of cell suspension were injected orthotopically into the anterior prostate lobe of CD1-nude mice (Charles River Laboratories, Wilmington, MA, USA). Orchidectomy was performed at the time of injection. Tumours were allowed to grow for ~6 weeks after injection and tumour growth was monitored weekly using a Vevo3100 ultrasound imaging system (Fujifilm Visualsonics, The Netherlands).

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Response regulation DECR1 participates in redox homeostasis by controlling the balance between saturated and unsaturated phospholipids. DECR1 knockout induces ER stress and sensitises castration-resistant prostate cancer (CRPC) cells to ferroptosis.
References
Ref 1 Human DECR1 is an androgen-repressed survival factor that regulates PUFA oxidation to protect prostate tumor cells from ferroptosis. Elife. 2020 Jul 20;9:e54166. doi: 10.7554/eLife.54166.
Ref 2 2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer. Nat Commun. 2020 May 19;11(1):2508. doi: 10.1038/s41467-020-16126-7.