Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10507)
Regulator Name 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)
Gene Name HMGCR
Gene ID 3156
Regulator Type Protein coding
Uniprot ID P04035
Sequence
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSS
DIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTG
LNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIG
VGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFAR
VLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKR
IEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVT
QKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNS
SLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYK
LETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGV
AGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRAC
DSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMI
SKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREV
LKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITL
MEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLAR
IVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA

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Family HMG-CoA reductase family
Function
Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis. HMGCR is the main target of statins, a class of cholesterol-lowering drugs.

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HGNC ID
HGNC:5006
KEGG ID hsa:3156
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
HMGCR 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
Browse Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [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 Breast cancer ICD-11: 2C60
 Disease Info 
Responsed Drug Simvastatin Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
In Vivo Model
MDA-MB-231 cells were injected to subcutaneous of mice to build a tumor model. When the tumor volume reaches about 60 mm3, all mice were randomly divided into five groups (n = 5) for various treatments. Then, mice were treated with PBS, Fe3O4@PCBMA, SIM, Fe3O4-SIM and Fe3O4@PCBMA-SIM through injected intravenously. The injected doses of SIM were 4 mg/kg body weight in each mouse on days 0, 3, 6, and 9.

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Response regulation The study presented the ferroptosis nanomedicine by loading simvastatin (SIM), a ferroptosis drugs, into zwitterionic polymer coated of magnetic nanoparticles (Fe3O4@PCBMA), thereby improving the therapeutic effect of triple negative breast cancer. SIM could inhibit the expression of HMGCR to downregulate the mevalonate (MVA) pathway and glutathione peroxidase 4 (GPX4), thereby inducing cancer cell ferroptosis.
Breast cancer [ICD-11: 2C60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) Protein coding
 Regulator Info 
Responsed Drug Simvastatin Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
In Vivo Model
MDA-MB-231 cells were injected to subcutaneous of mice to build a tumor model. When the tumor volume reaches about 60 mm3, all mice were randomly divided into five groups (n = 5) for various treatments. Then, mice were treated with PBS, Fe3O4@PCBMA, SIM, Fe3O4-SIM and Fe3O4@PCBMA-SIM through injected intravenously. The injected doses of SIM were 4 mg/kg body weight in each mouse on days 0, 3, 6, and 9.

    Click to Show/Hide
Response regulation The study presented the ferroptosis nanomedicine by loading simvastatin (SIM), a ferroptosis drugs, into zwitterionic polymer coated of magnetic nanoparticles (Fe3O4@PCBMA), thereby improving the therapeutic effect of triple negative breast cancer. SIM could inhibit the expression of HMGCR to downregulate the mevalonate (MVA) pathway and glutathione peroxidase 4 (GPX4), thereby inducing cancer cell ferroptosis.
Simvastatin [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
 Target Info 
Responsed Disease Breast cancer ICD-11: 2C60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model
 MCF-7 cells Breast carcinoma Homo sapiens CVCL_0031
MDA-MB-231 cells Breast adenocarcinoma Homo sapiens CVCL_0062
In Vivo Model
MDA-MB-231 cells were injected to subcutaneous of mice to build a tumor model. When the tumor volume reaches about 60 mm3, all mice were randomly divided into five groups (n = 5) for various treatments. Then, mice were treated with PBS, Fe3O4@PCBMA, SIM, Fe3O4-SIM and Fe3O4@PCBMA-SIM through injected intravenously. The injected doses of SIM were 4 mg/kg body weight in each mouse on days 0, 3, 6, and 9.

    Click to Show/Hide
Response regulation The study presented the ferroptosis nanomedicine by loading simvastatin (SIM), a ferroptosis drugs, into zwitterionic polymer coated of magnetic nanoparticles (Fe3O4@PCBMA), thereby improving the therapeutic effect of triple negative breast cancer. SIM could inhibit the expression of HMGCR to downregulate the mevalonate (MVA) pathway and glutathione peroxidase 4 (GPX4), thereby inducing cancer cell ferroptosis.
References
Ref 1 Simvastatin induced ferroptosis for triple-negative breast cancer therapy. J Nanobiotechnology. 2021 Oct 9;19(1):311. doi: 10.1186/s12951-021-01058-1.