m6A Target Gene Information

General Information of the m6A Target Gene (ID: M6ATAR00593)
Target Name Heat shock factor protein 1 (HSF1)
Synonyms
HSF 1; Heat shock transcription factor 1; HSTF 1
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Gene Name HSF1
Chromosomal Location 8q24.3
Family HSF family
Function
Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones heat shock proteins (HSPs) that protect cells from cellular insults' damage. In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form. Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes. Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival . Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form. Binds to inverted 5'-NGAAN-3' pentamer DNA sequences . Binds to chromatin at heat shock gene promoters. Plays also several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells. Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells in a symplekin (SYMPK)-dependent manner . Plays a role in nuclear export of stress-induced HSP70 mRNA. Plays a role in the regulation of mitotic progression. Plays also a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner. Involved in stress-induced cancer cell proliferation in a IER5-dependent manner; (Microbial infection) Plays a role in latent human immunodeficiency virus (HIV-1) transcriptional reactivation. Binds to the HIV-1 long terminal repeat promoter (LTR) to reactivate viral transcription by recruiting cellular transcriptional elongation factors, such as CDK9, CCNT1 and EP300.
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Gene ID 3297
Uniprot ID
HSF1_HUMAN
HGNC ID
HGNC:5224
Ensembl Gene ID
ENSG00000185122; ENSG00000284774
KEGG ID
hsa:3297
Full List of m6A Methylation Regulator of This Target Gene and Corresponding Disease/Drug Response(s)
HSF1 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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Fat mass and obesity-associated protein (FTO) [ERASER]
 Regulator Info 
Representative RNA-seq result indicating the expression of this target gene regulated by FTO
Cell Line NB4 cell line Homo sapiens
Treatment: shFTO NB4 cells
Control: shNS NB4 cells
 GSE103494
Regulation
logFC: -7.09E-01
p-value: 1.48E-02
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 FTO significantly promotes MM cell proliferation, migration, and invasion by targeting Heat shock factor protein 1 (HSF1)/HSPs in a YTHDF2-dependent manner. FTO inhibition, especially when combined with bortezomib (BTZ) treatment, synergistically inhibited myeloma bone tumor formation and extramedullary spread in NCG mice.
Target Regulation Up regulation
Responsed Disease Multiple myeloma ICD-11: 2A83.1
 Disease Info 
Responsed Drug Bortezomib Approved
 Drug Info 
In-vitro Model RPMI-8226 Plasma cell myeloma Homo sapiens CVCL_0014
MM1.R Plasma cell myeloma Homo sapiens CVCL_8794
In-vivo Model A total of 3×106 RPMI8226/MM1R-Luc cells were intravenously injected into NCG mice to establish a disseminated human MM xenograft model. The in vivo antitumor effect of the FTO inhibitor MA2 combined with or without the first-line chemotherapeutic agent BTZ was evaluated as follows: 3 days post xenotransplantation, MA2 (20 mg/kg), or vehicle control was injected intraperitoneally (i.p.) daily for 10 days, and BTZ was injected intraperitoneally on days 1, 4, 8, and 11. Mouse serum was collected at specified time points during the treatment, and the tumor burden was monitored by detecting myeloma cell-secreted Lambda light chains via a Human Lambda ELISA Kit (Bethyl Laboratories, No. E88-116). Tumor development was monitored weekly after treatment with an in vivo imaging system (IVIS, SI Imaging, Lago, and LagoX). Luciferin (150 mg/kg, YEASEN, Shanghai, China) was injected intraperitoneally into the mice.
Multiple myeloma [ICD-11: 2A83]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the m6A-centered Disease Response [1]
Response Summary FTO significantly promotes MM cell proliferation, migration, and invasion by targeting Heat shock factor protein 1 (HSF1)/HSPs in a YTHDF2-dependent manner. FTO inhibition, especially when combined with bortezomib (BTZ) treatment, synergistically inhibited myeloma bone tumor formation and extramedullary spread in NCG mice.
Responsed Disease Multiple myeloma [ICD-11: 2A83.1]
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Responsed Drug Bortezomib Approved
 Drug Info 
In-vitro Model RPMI-8226 Plasma cell myeloma Homo sapiens CVCL_0014
MM1.R Plasma cell myeloma Homo sapiens CVCL_8794
In-vivo Model A total of 3×106 RPMI8226/MM1R-Luc cells were intravenously injected into NCG mice to establish a disseminated human MM xenograft model. The in vivo antitumor effect of the FTO inhibitor MA2 combined with or without the first-line chemotherapeutic agent BTZ was evaluated as follows: 3 days post xenotransplantation, MA2 (20 mg/kg), or vehicle control was injected intraperitoneally (i.p.) daily for 10 days, and BTZ was injected intraperitoneally on days 1, 4, 8, and 11. Mouse serum was collected at specified time points during the treatment, and the tumor burden was monitored by detecting myeloma cell-secreted Lambda light chains via a Human Lambda ELISA Kit (Bethyl Laboratories, No. E88-116). Tumor development was monitored weekly after treatment with an in vivo imaging system (IVIS, SI Imaging, Lago, and LagoX). Luciferin (150 mg/kg, YEASEN, Shanghai, China) was injected intraperitoneally into the mice.
Bortezomib [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the m6A-centered Drug Response [1]
Response Summary FTO significantly promotes MM cell proliferation, migration, and invasion by targeting Heat shock factor protein 1 (HSF1)/HSPs in a YTHDF2-dependent manner. FTO inhibition, especially when combined with bortezomib (BTZ) treatment, synergistically inhibited myeloma bone tumor formation and extramedullary spread in NCG mice.
Target Regulator Fat mass and obesity-associated protein (FTO) ERASER
 Regulator Info 
Target Regulation Up regulation
Responsed Disease Multiple myeloma ICD-11: 2A83.1
 Disease Info 
In-vitro Model RPMI-8226 Plasma cell myeloma Homo sapiens CVCL_0014
MM1.R Plasma cell myeloma Homo sapiens CVCL_8794
In-vivo Model A total of 3×106 RPMI8226/MM1R-Luc cells were intravenously injected into NCG mice to establish a disseminated human MM xenograft model. The in vivo antitumor effect of the FTO inhibitor MA2 combined with or without the first-line chemotherapeutic agent BTZ was evaluated as follows: 3 days post xenotransplantation, MA2 (20 mg/kg), or vehicle control was injected intraperitoneally (i.p.) daily for 10 days, and BTZ was injected intraperitoneally on days 1, 4, 8, and 11. Mouse serum was collected at specified time points during the treatment, and the tumor burden was monitored by detecting myeloma cell-secreted Lambda light chains via a Human Lambda ELISA Kit (Bethyl Laboratories, No. E88-116). Tumor development was monitored weekly after treatment with an in vivo imaging system (IVIS, SI Imaging, Lago, and LagoX). Luciferin (150 mg/kg, YEASEN, Shanghai, China) was injected intraperitoneally into the mice.
References
Ref 1 FTO promotes multiple myeloma progression by posttranscriptional activation of HSF1 in an m(6)A-YTHDF2-dependent manner. Mol Ther. 2022 Mar 2;30(3):1104-1118. doi: 10.1016/j.ymthe.2021.12.012. Epub 2021 Dec 13.