General Information of the m6A Target Gene (ID: M6ATAR00707)
Target Name Breast cancer type 1 susceptibility protein (BRCA1)
Synonyms
RING finger protein 53; RING-type E3 ubiquitin transferase BRCA1
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Gene Name BRCA1
Chromosomal Location 17q21.31
Function
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage . Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator.
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Gene ID 672
Uniprot ID
BRCA1_HUMAN
HGNC ID
HGNC:1100
Ensembl Gene ID
ENSG00000012048
KEGG ID
hsa:672
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
BRCA1 can be regulated by the following regulator(s), and cause disease/drug response(s). You can browse detail information of regulator(s) or disease/drug response(s).
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RNA demethylase ALKBH5 (ALKBH5) [ERASER]
Representative RNA-seq result indicating the expression of this target gene regulated by ALKBH5
Cell Line HaCAT cell line Homo sapiens
Treatment: siALKBH5 HaCAT cells
Control: siControl HaCAT cells
GSE211076
Regulation
logFC: 7.57E-01
p-value: 2.32E-06
More Results Click to View More RNA-seq Results
In total 1 item(s) under this regulator
Experiment 1 Reporting the m6A Methylation Regulator of This Target Gene [1]
Response Summary ALKBH5 removed the m6A methylation of Breast cancer type 1 susceptibility protein (BRCA1) for mRNA stabilization and further enhanced DNA repair competency to decrease doxorubicin efficacy in breast cancer cells.
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
Responsed Drug Doxil Approved
In-vitro Model T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
HCC1937 Breast ductal carcinoma Homo sapiens CVCL_0290
In-vivo Model For the subcutaneously transplanted tumor model, wild-type, PRMT5-overexpressing or doxorubicin-resistant MDA-MB-231 cells (5 × 106 per mouse, n = 5-7 for each group) were diluted in 100 uL of phosphate-buffered saline (PBS) plus 100 uL of Matrigel (BD Biosciences) and subcutaneously injected into female nude mice to investigate tumor growth. When all tumor volumes reached 100 mm3, the mice were randomly assigned and treated with the indicated drugs. In the experiment, doxorubicin was administered once a week via intravenous tail vein injection at 2 mg/kg body weight, and tadalafil was administered daily via oral gavage at 2 mg/kg body weight. Tumor volume was measured every 3 days using a digital caliper and calculated using the formula V = 1/2 × (diameter) × (smaller diameter)2. The mice were euthanized 27 days after injection.
Breast cancer [ICD-11: 2C60]
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary ALKBH5 removed the m6A methylation of Breast cancer type 1 susceptibility protein (BRCA1) for mRNA stabilization and further enhanced DNA repair competency to decrease doxorubicin efficacy in breast cancer cells.
Responsed Disease Breast cancer [ICD-11: 2C60]
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Responsed Drug Doxil Approved
In-vitro Model T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
HCC1937 Breast ductal carcinoma Homo sapiens CVCL_0290
In-vivo Model For the subcutaneously transplanted tumor model, wild-type, PRMT5-overexpressing or doxorubicin-resistant MDA-MB-231 cells (5 × 106 per mouse, n = 5-7 for each group) were diluted in 100 uL of phosphate-buffered saline (PBS) plus 100 uL of Matrigel (BD Biosciences) and subcutaneously injected into female nude mice to investigate tumor growth. When all tumor volumes reached 100 mm3, the mice were randomly assigned and treated with the indicated drugs. In the experiment, doxorubicin was administered once a week via intravenous tail vein injection at 2 mg/kg body weight, and tadalafil was administered daily via oral gavage at 2 mg/kg body weight. Tumor volume was measured every 3 days using a digital caliper and calculated using the formula V = 1/2 × (diameter) × (smaller diameter)2. The mice were euthanized 27 days after injection.
Doxil [Approved]
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary ALKBH5 removed the m6A methylation of Breast cancer type 1 susceptibility protein (BRCA1) for mRNA stabilization and further enhanced DNA repair competency to decrease doxorubicin efficacy in breast cancer cells.
Target Regulator RNA demethylase ALKBH5 (ALKBH5) ERASER
Target Regulation Up regulation
Responsed Disease Breast cancer ICD-11: 2C60
In-vitro Model T-47D Invasive breast carcinoma Homo sapiens CVCL_0553
MDA-MB-231 Breast adenocarcinoma Homo sapiens CVCL_0062
MCF-7 Invasive breast carcinoma Homo sapiens CVCL_0031
HCC1937 Breast ductal carcinoma Homo sapiens CVCL_0290
In-vivo Model For the subcutaneously transplanted tumor model, wild-type, PRMT5-overexpressing or doxorubicin-resistant MDA-MB-231 cells (5 × 106 per mouse, n = 5-7 for each group) were diluted in 100 uL of phosphate-buffered saline (PBS) plus 100 uL of Matrigel (BD Biosciences) and subcutaneously injected into female nude mice to investigate tumor growth. When all tumor volumes reached 100 mm3, the mice were randomly assigned and treated with the indicated drugs. In the experiment, doxorubicin was administered once a week via intravenous tail vein injection at 2 mg/kg body weight, and tadalafil was administered daily via oral gavage at 2 mg/kg body weight. Tumor volume was measured every 3 days using a digital caliper and calculated using the formula V = 1/2 × (diameter) × (smaller diameter)2. The mice were euthanized 27 days after injection.
References
Ref 1 PRMT5 regulates RNA m6A demethylation for doxorubicin sensitivity in breast cancer. Mol Ther. 2022 Jul 6;30(7):2603-2617. doi: 10.1016/j.ymthe.2022.03.003. Epub 2022 Mar 10.