Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10221)

Regulator Name	ELAV-like protein 1 (ELAVL1)
Synonyms	HUR; Hu-antigen R Click to Show/Hide
Gene Name	ELAVL1
Gene ID	1994
Regulator Type	Protein coding
Uniprot ID	Q15717
Sequence	MSNGYEDHMAEDCRGDIGRTNLIVNYLPQNMTQDELRSLFSSIGEVESAKLIRDKVAGHS LGYGFVNYVTAKDAERAINTLNGLRLQSKTIKVSYARPSSEVIKDANLYISGLPRTMTQK DVEDMFSRFGRIINSRVLVDQTTGLSRGVAFIRFDKRSEAEEAITSFNGHKPPGSSEPIT VKFAANPNQNKNVALLSQLYHSPARRFGGPVHHQAQRFRFSPMGVDHMSGLSGVNVPGNA SSGWCIFIYNLGQDADEGILWQMFGPFGAVTNVKVIRDFNTNKCKGFGFVTMTNYEEAAM AIASLNGYRLGDKILQVSFKTNKSHK Click to Show/Hide
Family	RRM elav family
Function	RNA-binding protein that binds to the 3'-UTR region of mRNAs and increases their stability. Involved in embryonic stem cell (ESC) differentiation: preferentially binds mRNAs that are not methylated by N6-methyladenosine (m6A), stabilizing them, promoting ESC differentiation. Has also been shown to be capable of binding to m6A-containing mRNAs and contributes to MYC stability by binding to m6A-containing MYC mRNAs. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs. Binds avidly to the AU-rich element in FOS and IL3/interleukin-3 mRNAs. In the case of the FOS AU-rich element, binds to a core element of 27 nucleotides that contain AUUUA, AUUUUA, and AUUUUUA motifs. Binds preferentially to the 5'-UUUU[AG]UUU-3' motif in vitro. With ZNF385A, binds the 3'-UTR of p53/TP53 mRNA to control their nuclear export induced by CDKN2A. Hence, may regulate p53/TP53 expression and mediate in part the CDKN2A anti-proliferative activity. May also bind with ZNF385A the CCNB1 mRNA. Increases the stability of the leptin mRNA harboring an AU-rich element (ARE) in its 3' UTR. Click to Show/Hide
HGNC ID	HGNC:3312
KEGG ID	hsa:1994

Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)

ELAVL1 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).

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Nuclear receptor coactivator 4 (NCOA4) [Driver]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator			[1]
Target for Ferroptosis	Driver
Responsed Disease	Liver fibrosis	ICD-11: DB93	Disease Info
Responsed Drug	Sorafenib	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
	Autophagy		hsa04140
	Ubiquitin mediated proteolysis		hsa04120
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	hHSCs (Human hepatic stellate cells)
In Vivo Model	Eight-week-old male C57BL/6 mice were purchased from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Sorafenib (10 mg/kg, once every other day) was suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. The livers were collected 2 weeks after surgery under general anesthesia. Click to Show/Hide
Response regulation	Sorafenib treatment remarkably upregulated NCOA4 expression, and 3 critical events including ELAVL1 upregulation, ferritinophagy activation, and ferroptosis induction occur in primary human HSCs from fibrotic patients receiving sorafenib monotherapy. ELAVL1 is a potential target for the treatment of liver fibrosis.

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				[2]
Target for Ferroptosis	Suppressor
Responsed Disease	Cerebral ischaemic stroke		ICD-11: 8B11	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC12 cells	Adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_0481
In Vivo Model	Rats were placed on a heating panel after anesthetized with pentobarbital sodium (30 mg/kg). We operated the intraluminal middle cerebral artery occlusion (MCAO) to establish the focal cerebral ischemia. Then 2 h later, we established the reperfusion. In brief, the left internal carotid artery of the rats was isolated. Then the ligation of middle cerebral artery was performed by a 4/0 surgical nylon monofilament to occlude the blood flow. 2 h later, we removed the filament to restore the blood reperfusion for 24 h. Click to Show/Hide
Response regulation	ELAVL1 silencing observably facilitated cell viability, GSH content, GPX4 and SLC7A11 expression. ELAVL1 plays a critical role in protecting against ferroptosis-induced cerebral I/R and subsequent brain damage via DNMT3B/PINK1 axis, thus providing a new potential target for ischemic stroke treatment.

Cystine/glutamate transporter (SLC7A11) [Driver; Suppressor]

Target Info

In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[3]
Target for Ferroptosis	Suppressor
Responsed Disease	Gastric cancer		ICD-11: 2B72	Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	AGS cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MGC-803 cells	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
In Vivo Model	For animal models of gastric subserosal injection, we collected MGC-803 cell lines (5 x 10 cells) that were infected by lentivirus with or without PMAN-OE, and suspended in 40 ul serum-free medium (50% Matrigel). After that, nude mice (six mice per group) were anesthetized by intraperitoneal injection of 100 ul of pentobarbital (1%). After disinfection, the abdominal cavity was opened to expose the greater curvature of the stomach. The tumor suspension (40 ul) was implanted under the serosa of the greater curvature of the stomach of the nude mice through an insulin needle. Click to Show/Hide
Response regulation	HIF-1 could act as a protective factor against ferroptosis in gastric cancer (GC) cells. HIF-1 activates PMAN at the transcriptional level, which greatly improves the output of ELAVL1 in the cytoplasm. ELAVL1 directly combines with the AREs of SLC7A11 mRNA 3-UTR and improves the stability of SLC7A11mRNA, thereby increasing the expression of SLC7A11 and reducing the accumulation of ROS and iron in ferroptosis, ultimately promoting the proliferation and development of tumor cells.

Unspecific Target [Unspecific Target]

In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator				[4]
Responsed Disease	Lung cancer		ICD-11: 2C25	Disease Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	NCI-H358 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	SPC-A1 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
Response regulation	LSH induces ELAVL1 expression through the inactivation of p53 and ELAVL1 enhances LINC00336 levels through transcriptional regulation by interacting with LINC00336. Then, LINC00336 absorbs MIR6852 as a ceRNA, which increases the mRNA level of CBS, stimulating cell proliferation, colony formation, and tumor formation, and inhibiting ferroptosis in lung cancer.
Experiment 2 Reporting the Ferroptosis Target of This Regulator				[5]
Responsed Disease	Ischemia/reperfusion injury		ICD-11: DB98	Disease Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
	Autophagy			hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	hCMs (Human cardiomyocytes)
In Vivo Model	Healthy male C57BL/6J mice (8 weeks) were purchased from Shanghai SLAC laboratory Animal Co., Ltd. (Shanghai, China) and kept in the standard animal facility. To induce myocardial I/R injury, mice were anesthetized by ketamine and xylazine (250 and 10 mg/kg, respectively) first and maintained on 3% isoflurane. An abdominal incision was made around the fourth intercostal space and the left anterior descending coronary artery (LAD) was exposed. LAD was ligated with the silk suture for 1 h followed by 4 h of perfusion. During the perfusion, the incision was closed. For the sham group, same surgery procedures were performed without any ligation. For inhibition of ELAVL1 or overexpression of Beclin-1 in mice, lentivirus vectors (1 x 10⁸ titers) obtained from GeneChem (Shanghai, China) were used for left ventricular cavity injection. After 7 days of lentivirus infection, mice were subjected to myocardial I/R surgery. Click to Show/Hide
Response regulation	FOXC1 transcriptionally activated ELAVL1 may promote ferroptosis during myocardial ischemia and reperfusion (I/R) injury by modulating autophagy, leading to myocardial injury. Inhibition of ELAVL1-mediated autophagic ferroptosis would be a new viewpoint in the treatment of myocardial I/R injury.

Liver fibrosis [ICD-11: DB93]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response			[1]
Target Regulator	ELAV-like protein 1 (ELAVL1)	Protein coding	Regulator Info
Responsed Drug	Sorafenib	Investigative	Drug Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
	Autophagy		hsa04140
	Ubiquitin mediated proteolysis		hsa04120
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	hHSCs (Human hepatic stellate cells)
In Vivo Model	Eight-week-old male C57BL/6 mice were purchased from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Sorafenib (10 mg/kg, once every other day) was suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. The livers were collected 2 weeks after surgery under general anesthesia. Click to Show/Hide
Response regulation	Sorafenib treatment remarkably upregulated NCOA4 expression, and 3 critical events including ELAVL1 upregulation, ferritinophagy activation, and ferroptosis induction occur in primary human HSCs from fibrotic patients receiving sorafenib monotherapy. ELAVL1 is a potential target for the treatment of liver fibrosis.

Gastric cancer [ICD-11: 2B72]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[3]
Target Regulator	ELAV-like protein 1 (ELAVL1)		Protein coding	Regulator Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
	Cell proliferation
In Vitro Model	AGS cells	Gastric adenocarcinoma	Homo sapiens	CVCL_0139
	MGC-803 cells	Gastric mucinous adenocarcinoma	Homo sapiens	CVCL_5334
In Vivo Model	For animal models of gastric subserosal injection, we collected MGC-803 cell lines (5 x 10 cells) that were infected by lentivirus with or without PMAN-OE, and suspended in 40 ul serum-free medium (50% Matrigel). After that, nude mice (six mice per group) were anesthetized by intraperitoneal injection of 100 ul of pentobarbital (1%). After disinfection, the abdominal cavity was opened to expose the greater curvature of the stomach. The tumor suspension (40 ul) was implanted under the serosa of the greater curvature of the stomach of the nude mice through an insulin needle. Click to Show/Hide
Response regulation	HIF-1 could act as a protective factor against ferroptosis in gastric cancer (GC) cells. HIF-1 activates PMAN at the transcriptional level, which greatly improves the output of ELAVL1 in the cytoplasm. ELAVL1 directly combines with the AREs of SLC7A11 mRNA 3-UTR and improves the stability of SLC7A11mRNA, thereby increasing the expression of SLC7A11 and reducing the accumulation of ROS and iron in ferroptosis, ultimately promoting the proliferation and development of tumor cells.

Cerebral ischaemic stroke [ICD-11: 8B11]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[2]
Target Regulator	ELAV-like protein 1 (ELAVL1)		Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism			hsa01212
	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
In Vitro Model	PC12 cells	Adrenal gland pheochromocytoma	Rattus norvegicus	CVCL_0481
In Vivo Model	Rats were placed on a heating panel after anesthetized with pentobarbital sodium (30 mg/kg). We operated the intraluminal middle cerebral artery occlusion (MCAO) to establish the focal cerebral ischemia. Then 2 h later, we established the reperfusion. In brief, the left internal carotid artery of the rats was isolated. Then the ligation of middle cerebral artery was performed by a 4/0 surgical nylon monofilament to occlude the blood flow. 2 h later, we removed the filament to restore the blood reperfusion for 24 h. Click to Show/Hide
Response regulation	ELAVL1 silencing observably facilitated cell viability, GSH content, GPX4 and SLC7A11 expression. ELAVL1 plays a critical role in protecting against ferroptosis-induced cerebral I/R and subsequent brain damage via DNMT3B/PINK1 axis, thus providing a new potential target for ischemic stroke treatment.

Lung cancer [ICD-11: 2C25]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response				[4]
Target Regulator	ELAV-like protein 1 (ELAVL1)		Protein coding	Regulator Info
Pathway Response	Ferroptosis			hsa04216
Cell Process	Cell ferroptosis
Cell Process	Cell proliferation
In Vitro Model	NCI-H358 cells	Minimally invasive lung adenocarcinoma	Homo sapiens	CVCL_1559
	PC-9 cells	Lung adenocarcinoma	Homo sapiens	CVCL_B260
	A-549 cells	Lung adenocarcinoma	Homo sapiens	CVCL_0023
	SPC-A1 cells	Endocervical adenocarcinoma	Homo sapiens	CVCL_6955
Response regulation	LSH induces ELAVL1 expression through the inactivation of p53 and ELAVL1 enhances LINC00336 levels through transcriptional regulation by interacting with LINC00336. Then, LINC00336 absorbs MIR6852 as a ceRNA, which increases the mRNA level of CBS, stimulating cell proliferation, colony formation, and tumor formation, and inhibiting ferroptosis in lung cancer.

Ischemia/reperfusion injury [ICD-11: DB98]

Disease Info

In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response			[5]
Target Regulator	ELAV-like protein 1 (ELAVL1)	Protein coding	Regulator Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
	Autophagy		hsa04140
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	hCMs (Human cardiomyocytes)
In Vivo Model	Healthy male C57BL/6J mice (8 weeks) were purchased from Shanghai SLAC laboratory Animal Co., Ltd. (Shanghai, China) and kept in the standard animal facility. To induce myocardial I/R injury, mice were anesthetized by ketamine and xylazine (250 and 10 mg/kg, respectively) first and maintained on 3% isoflurane. An abdominal incision was made around the fourth intercostal space and the left anterior descending coronary artery (LAD) was exposed. LAD was ligated with the silk suture for 1 h followed by 4 h of perfusion. During the perfusion, the incision was closed. For the sham group, same surgery procedures were performed without any ligation. For inhibition of ELAVL1 or overexpression of Beclin-1 in mice, lentivirus vectors (1 x 10⁸ titers) obtained from GeneChem (Shanghai, China) were used for left ventricular cavity injection. After 7 days of lentivirus infection, mice were subjected to myocardial I/R surgery. Click to Show/Hide
Response regulation	FOXC1 transcriptionally activated ELAVL1 may promote ferroptosis during myocardial ischemia and reperfusion (I/R) injury by modulating autophagy, leading to myocardial injury. Inhibition of ELAVL1-mediated autophagic ferroptosis would be a new viewpoint in the treatment of myocardial I/R injury.

Sorafenib [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	Nuclear receptor coactivator 4 (NCOA4)	Driver	Target Info
Responsed Disease	Liver fibrosis	ICD-11: DB93	Disease Info
Pathway Response	Fatty acid metabolism		hsa01212
	Ferroptosis		hsa04216
	Autophagy		hsa04140
	Ubiquitin mediated proteolysis		hsa04120
Cell Process	Cell ferroptosis
	Cell autophagy
In Vitro Model	hHSCs (Human hepatic stellate cells)
In Vivo Model	Eight-week-old male C57BL/6 mice were purchased from the Experimental Animal Center of Yangzhou University (Yangzhou, China). Sorafenib (10 mg/kg, once every other day) was suspended in sterile phosphate-buffered saline (PBS; Sigma, P5368) and given by intraperitoneal injection for 2 weeks after the BDL operation. The livers were collected 2 weeks after surgery under general anesthesia. Click to Show/Hide
Response regulation	Sorafenib treatment remarkably upregulated NCOA4 expression, and 3 critical events including ELAVL1 upregulation, ferritinophagy activation, and ferroptosis induction occur in primary human HSCs from fibrotic patients receiving sorafenib monotherapy. ELAVL1 is a potential target for the treatment of liver fibrosis.

References

Ref 1	Activation of ferritinophagy is required for the RNA-binding protein ELAVL1/HuR to regulate ferroptosis in hepatic stellate cells. Autophagy. 2018;14(12):2083-2103. doi: 10.1080/15548627.2018.1503146. Epub 2018 Aug 21.
Ref 2	Downregulation of ELAVL1 attenuates ferroptosis-induced neuronal impairment in rats with cerebral ischemia/reperfusion via reducing DNMT3B-dependent PINK1 methylation. Metab Brain Dis. 2022 Dec;37(8):2763-2775. doi: 10.1007/s11011-022-01080-8. Epub 2022 Sep 29.
Ref 3	Corrigendum to "Hypoxia-induced HIF-1/lncRNA-PMAN inhibits ferroptosis by promoting the cytoplasmic translocation of ELAVL1 in peritoneal dissemination from gastric cancer" [Redox Biol. 52C (2022) 102312]. Redox Biol. 2022 Sep;55:102402. doi: 10.1016/j.redox.2022.102402. Epub 2022 Jul 19.
Ref 4	Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA. Cell Death Differ. 2019 Nov;26(11):2329-2343. doi: 10.1038/s41418-019-0304-y. Epub 2019 Feb 20.
Ref 5	ELAVL1 is transcriptionally activated by FOXC1 and promotes ferroptosis in myocardial ischemia/reperfusion injury by regulating autophagy. Mol Med. 2021 Feb 10;27(1):14. doi: 10.1186/s10020-021-00271-w.

Ferroptosis Regulator Information

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Correspondence

Prof. Shuiping Liu