Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10134)
Regulator Name Ribonucleoside-diphosphate reductase subunit M2 (RRM2)
Synonyms
RR2; Ribonucleotide reductase small chain; Ribonucleotide reductase small subunit
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Gene Name RRM2
Gene ID 6241
Regulator Type Protein coding
Uniprot ID P31350
Sequence
MLSLRVPLAPITDPQQLQLSPLKGLSLVDKENTPPALSGTRVLASKTARRIFQEPTEPKT
KAAAPGVEDEPLLRENPRRFVIFPIEYHDIWQMYKKAEASFWTAEEVDLSKDIQHWESLK
PEERYFISHVLAFFAASDGIVNENLVERFSQEVQITEARCFYGFQIAMENIHSEMYSLLI
DTYIKDPKEREFLFNAIETMPCVKKKADWALRWIGDKEATYGERVVAFAAVEGIFFSGSF
ASIFWLKKRGLMPGLTFSNELISRDEGLHCDFACLMFKHLVHKPSEERVREIIINAVRIE
QEFLTEALPVKLIGMNCTLMKQYIEFVADRLMLELGFSKVFRVENPFDFMENISLEGKTN
FFEKRVGEYQRMGVMSSPTENSFTLDADF

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Family Ribonucleoside diphosphate reductase small chain family
Function
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides. Inhibits Wnt signaling.

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HGNC ID
HGNC:10452
KEGG ID hsa:6241
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
RRM2 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 Hepatocellular carcinoma ICD-11: 2C12
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
BEL-7402 cells Endocervical adenocarcinoma Homo sapiens CVCL_5492
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
BEL-7404 cells Endocervical adenocarcinoma Homo sapiens CVCL_6568
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Response regulation RRM2 exerts an anti-ferroptotic role in liver cancer cells by sustaining GSH synthesis. Serum RRM2 will be useful as a biomarker to evaluate the degree to which ferroptosis is suppressed and improve diagnostic efficiency for liver cancer.
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 infiltration
In Vitro Model
 LL/2 (LLC1) cells Lung cancer Mus musculus CVCL_4358
hBMDMs (Human bone marrow-derived macrophages)
In Vivo Model
LLC cells were cultured to prepare a single-cell suspension in PBS, and then 5 x 10^6 LLC cells were injected subcutaneously into C57/B6 male mice (Shanghai Slac Laboratory Animal Co. LTD, China) aged 8 weeks. Every group of mice consisted of 6 randomly assigned mice. When the tumor size was visible, the tumor size was measured once every three days until it reached 1000 mm3.

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Response regulation Combined with lung adenocarcinoma tissue samples and mouse trials, RRM2 was found to influence lung cancer progression and affect tumor immune cell infiltration. RRM2 inhibition effectively promoted M1 macrophage polarization and suppressed M2 macrophage polarization in vitro and in vivo.
Hepatocellular carcinoma [ICD-11: 2C12]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Ribonucleoside-diphosphate reductase subunit M2 (RRM2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
BEL-7402 cells Endocervical adenocarcinoma Homo sapiens CVCL_5492
SMMC-7721 cells Endocervical adenocarcinoma Homo sapiens CVCL_0534
SK-HEP-1 cells Liver and intrahepatic bile duct epithelial neoplasm Homo sapiens CVCL_0525
Huh-7 cells Hepatocellular carcinoma Homo sapiens CVCL_0336
BEL-7404 cells Endocervical adenocarcinoma Homo sapiens CVCL_6568
Hep-G2 cells Hepatoblastoma Homo sapiens CVCL_0027
Response regulation RRM2 exerts an anti-ferroptotic role in liver cancer cells by sustaining GSH synthesis. Serum RRM2 will be useful as a biomarker to evaluate the degree to which ferroptosis is suppressed and improve diagnostic efficiency for liver cancer.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Ribonucleoside-diphosphate reductase subunit M2 (RRM2) Protein coding
 Regulator Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell infiltration
In Vitro Model
 LL/2 (LLC1) cells Lung cancer Mus musculus CVCL_4358
hBMDMs (Human bone marrow-derived macrophages)
In Vivo Model
LLC cells were cultured to prepare a single-cell suspension in PBS, and then 5 x 10^6 LLC cells were injected subcutaneously into C57/B6 male mice (Shanghai Slac Laboratory Animal Co. LTD, China) aged 8 weeks. Every group of mice consisted of 6 randomly assigned mice. When the tumor size was visible, the tumor size was measured once every three days until it reached 1000 mm3.

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Response regulation Combined with lung adenocarcinoma tissue samples and mouse trials, RRM2 was found to influence lung cancer progression and affect tumor immune cell infiltration. RRM2 inhibition effectively promoted M1 macrophage polarization and suppressed M2 macrophage polarization in vitro and in vivo.
References
Ref 1 RRM2 protects against ferroptosis and is a tumor biomarker for liver cancer. Cancer Cell Int. 2020 Dec 7;20(1):587. doi: 10.1186/s12935-020-01689-8.
Ref 2 Identification of critical ferroptosis regulators in lung adenocarcinoma that RRM2 facilitates tumor immune infiltration by inhibiting ferroptotic death. Clin Immunol. 2021 Nov;232:108872. doi: 10.1016/j.clim.2021.108872. Epub 2021 Oct 11.