General Information of the Disease (ID: DIS00042)
Name
Cervical cancer
ICD
ICD-11: 2C77
Full List of Target(s) of This Ferroptosis-centered Disease
Heat shock protein beta-1 (HSPB1)
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Endocervical adenocarcinoma [ICD-11: 2C77]
Responsed Drug Erastin Investigative
Responsed Regulator Heat shock factor protein 1 (HSF1) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
LNCaP cells Prostate carcinoma Homo sapiens CVCL_0395
In Vivo Model
Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection.

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Response regulation Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 ( HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Endocervical adenocarcinoma [ICD-11: 2C77]
Responsed Drug Erastin Investigative
Responsed Regulator Heat shock factor protein 1 (HSF1) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
U2OS cells Osteosarcoma Homo sapiens CVCL_0042
LNCaP cells Prostate carcinoma Homo sapiens CVCL_0395
In Vivo Model
Indicated HeLa cells were subcutaneously injected into the dorsal flanks right of the midline in SCID mice (weight ~20 g). At day seven, mice were injected with erastin (20 mg/kg/ i.v., twice daily every other day) with or without KRIBB3 (50 mg/kg/ i.p., once daily every other day) for two weeks. Erastin was dissolved in vehicle (2% DMSO and 98% phosphate buffered saline) and prepared by Ultrasonic Cleaner (Fisher Scientific). A final volume of 300 ul erastin was applied through the tail vein. The Rodent Tail Vein Catheter (Braintree Scientific, MTV#1) were used to perform injection.

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Response regulation Erastin, a specific ferroptosis-inducing compound, stimulates heat shock factor 1 (HSF1)-dependent HSPB1 expression in endocervical adenocarcinoma cells. Knockdown of HSF1 and HSPB1 enhances erastin-induced ferroptosis, whereas heat shock pretreatment and overexpression of HSPB1 inhibits erastin-induced ferroptosis.
Cytochrome b-245 heavy chain (CYBB)
In total 5 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Endocervical adenocarcinoma [ICD-11: 2C77]
Responsed Drug Hydrogen Peroxide Investigative
Responsed Regulator Aquaporin-3 (AQP3) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs( AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Endocervical adenocarcinoma [ICD-11: 2C77]
Responsed Drug Hydrogen Peroxide Investigative
Responsed Regulator Aquaporin-5 (AQP5) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Endocervical adenocarcinoma [ICD-11: 2C77]
Responsed Drug Hydrogen Peroxide Investigative
Responsed Regulator Aquaporin-8 (AQP8) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5, AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Endocervical adenocarcinoma [ICD-11: 2C77]
Responsed Drug Hydrogen Peroxide Investigative
Responsed Regulator Aquaporin-8 (AQP8) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Experiment 5 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Driver
Responsed Disease Endocervical adenocarcinoma [ICD-11: 2C77]
Responsed Drug Hydrogen Peroxide Investigative
Responsed Regulator Aquaporin-3 (AQP3) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Mitochondrial transfer upregulated the mitochondrial quality control protein prohibitin 2 (PHB2), which contributes to reduced AQPs(AQP3, AQP5,AQP8) expression. H2O2 treatment enhances AQPs expression, Fe2+ level, and lipid peroxidation, and decrease mitochondrial function by downregulating PHB2 in endocervical adenocarcinoma, and thus, is a promising modality for effective cancer treatment. Moreover, NOX2 expression is upregulated in 0 cells, and that NOX2 binds to AQP3, 5, and 8 in both HeLa and SAS cells.
Polyunsaturated fatty acid lipoxygenase ALOX12 (ALOX12)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Driver
Responsed Disease Endocervical adenocarcinoma [ICD-11: 2C77]
Responsed Regulator hsa-miR-7-5p (miRNA) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SAS cells Tongue squamous cell carcinoma Homo sapiens CVCL_1675
Response regulation Knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe2+amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount in Endocervical adenocarcinoma.
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Target for Ferroptosis Suppressor
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Drug Dihydroartemisinin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
Response regulation Dihydroartemisinin (DHA) treatment initiated ferroptosis, as evidenced by the accumulation of reactive oxygen species (ROS), malondialdehyde (MDA) and liquid peroxidation (LPO) levels and simultaneously depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). Moreover, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy was also induced by DHA leading to subsequent increases of intracellular labile iron pool (LIP), exacerbated the Fenton reaction resulting in excessive ROS production, and enhanced cervical cancer ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Target for Ferroptosis Suppressor
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator hsa-miR-193a-5p (miRNA) Driver
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response regulation miR-193a-5p was able to target GPX4 and circACAP2 promoted GPX4 expression by sponging miR-193a-5p in cervical cancer cells.Therefore, we concluded that circular RNA circACAP2 repressed ferroptosis of cervical cancer during malignant progression by miR-193a-5p/GPX4.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Target for Ferroptosis Suppressor
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator CircACAP2 (circRNA) Suppressor
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response regulation miR-193a-5p was able to target GPX4 and circACAP2 promoted GPX4 expression by sponging miR-193a-5p in cervical cancer cells.Therefore, we concluded that circular RNA circACAP2 repressed ferroptosis of cervical cancer during malignant progression by miR-193a-5p/GPX4.
Nuclear receptor coactivator 4 (NCOA4)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Target for Ferroptosis Driver
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Drug Dihydroartemisinin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
Response regulation Dihydroartemisinin (DHA) treatment initiated ferroptosis, as evidenced by the accumulation of reactive oxygen species (ROS), malondialdehyde (MDA) and liquid peroxidation (LPO) levels and simultaneously depletion of glutathione peroxidase 4 (GPX4) and glutathione (GSH). Moreover, nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy was also induced by DHA leading to subsequent increases of intracellular labile iron pool (LIP), exacerbated the Fenton reaction resulting in excessive ROS production, and enhanced cervical cancer ferroptosis.
Long-chain-fatty-acid--CoA ligase 4 (ACSL4)
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [6]
Target for Ferroptosis Driver
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Drug Oleanolic acid Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
In Vivo Model
Male BALB/c Nude mice (20 ± 2g, 5 weeks old) were supplied by Hangzhou Ziyuan Experimental Animal Technology Co. LTD (SYXK-20180049) for this study. The nude mice were kept under specefic pathogen free (SPF) conditions for one week, and 5x107 Hela cells were injected under the left axillary skin after acclimatization. The tumors of Hela cell-inoculated mice were measured every 3 days after modeling, and tumor>=0.5 cm in diameter were considered successful. The tumor-bearing mice were randomly divided into control group (n = 6), 40 mg/kg OA group (n = 6) and 80 mg/kg OA group (n = 6). 40 mg/kg OA group and 80 mg/kg OA group both received subcutaneous injection modeling and control mice received saline intraperitoneal injections. The 40 mg/kg OA group and 80 mg/kg OA group received daily intraperitoneal injections of 40 mg/kg OA and 80 mg/kg OA for 15 days.

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Response regulation Oleanolic acid (OA) significantly reduced the viability and proliferative capacity of Hela cells. OA activated ferroptosis in Hela cells by promoting ACSL4 expression, thereby reducing the survival rate of Hela cells. Therefore, promotion of ACSL4-dependent ferroptosis by OA may be a potential approach for the treatment of cervical cancer.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Target for Ferroptosis Driver
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator CircLMO1 (circRNA) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell invasion
In Vitro Model SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Ca Ski cells Cervical squamous cell carcinoma Homo sapiens CVCL_1100
C33A cells Cervical squamous cell carcinoma Homo sapiens CVCL_1094
In Vivo Model
Male BALB/c nude mice (6 weeks old) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). The mice were kept in a constant temperature (25) and pathogen-free room with free access to food and water ad libitum. The animal experiments were approved by the Ethics Committee for Animal Experimentation of The Second Affiliated Hospital and Yuying Childrens Hospital. Mice were euthanised with isoflurane inhalation. CaSki cells overexpressing circLMO1 (7 x 106 cells/100 uL PBS) were injected subcutaneously into the flank of mice. Tumor growth was measured with a caliper 3 times a week and tumor-bearing mice were euthanised at 5 weeks after inoculation.

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Response regulation CircLMO1 acted as a competing endogenous RNA (ceRNA) by sponging miR-4192 to repress target gene ACSL4. CircLMO1 promoted cervical cancer cell ferroptosis through up-regulating ACSL4 expression. Overexpression of miR-4291 or knockdown of ACSL4 reversed the effect of circLMO1 on facilitating ferroptosis and repressing cervical cancer cell proliferation and invasion.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Target for Ferroptosis Driver
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator hsa-miR-4291 (miRNA) Suppressor
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell invasion
In Vitro Model SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Ca Ski cells Cervical squamous cell carcinoma Homo sapiens CVCL_1100
C33A cells Cervical squamous cell carcinoma Homo sapiens CVCL_1094
In Vivo Model
Male BALB/c nude mice (6 weeks old) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). The mice were kept in a constant temperature (25) and pathogen-free room with free access to food and water ad libitum. The animal experiments were approved by the Ethics Committee for Animal Experimentation of The Second Affiliated Hospital and Yuying Childrens Hospital. Mice were euthanised with isoflurane inhalation. CaSki cells overexpressing circLMO1 (7 x 106 cells/100 uL PBS) were injected subcutaneously into the flank of mice. Tumor growth was measured with a caliper 3 times a week and tumor-bearing mice were euthanised at 5 weeks after inoculation.

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Response regulation CircLMO1 acted as a competing endogenous RNA (ceRNA) by sponging miR-4192 to repress target gene ACSL4. CircLMO1 promoted cervical cancer cell ferroptosis through up-regulating ACSL4 expression. Overexpression of miR-4291 or knockdown of ACSL4 reversed the effect of circLMO1 on facilitating ferroptosis and repressing cervical cancer cell proliferation and invasion.
Cystine/glutamate transporter (SLC7A11)
In total 4 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [8]
Target for Ferroptosis Suppressor
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator CircEPSTI1 (circRNA) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Ca Ski cells Cervical squamous cell carcinoma Homo sapiens CVCL_1100
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
hCECs (Human cervical epithelial cells)
In Vivo Model
The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 107 cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured.

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Response regulation CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1-miR-375/409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [8]
Target for Ferroptosis Suppressor
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator hsa-miR-375-3p (miRNA) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Ca Ski cells Cervical squamous cell carcinoma Homo sapiens CVCL_1100
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
hCECs (Human cervical epithelial cells)
In Vivo Model
The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 107 cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured.

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Response regulation CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1- miR-375/409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [8]
Target for Ferroptosis Suppressor
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator hsa-miR-409-3p (miRNA) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Ca Ski cells Cervical squamous cell carcinoma Homo sapiens CVCL_1100
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
hCECs (Human cervical epithelial cells)
In Vivo Model
The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 107 cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured.

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Response regulation CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1-miR-375/ 409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis.
Experiment 4 Reporting the Ferroptosis-centered Disease Response by This Target [8]
Target for Ferroptosis Suppressor
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator hsa-miR-515-5p (miRNA) Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model Ca Ski cells Cervical squamous cell carcinoma Homo sapiens CVCL_1100
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
hCECs (Human cervical epithelial cells)
In Vivo Model
The 4-week-old female BALB/c nude mice were used for constructing xenograft model. HeLa cells (1 x 107 cells/mL) were injected into the dorsal flanksusing using 1-mL syringes. Then tumor size was measured and mice received intertumoral injection of si-crEPSTI1-1 (40 uL siRNA1 for cicrEPSTI1) and negative control (40 uL negative control) every four days, respectively (5 mice/group). After 28 days, the mice were sacrificed and xenografts were measured.

    Click to Show/Hide
Response regulation CircEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. CircEPSTI1-miR-375/409-3P/ 515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis.
Unspecific Target
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [9]
Responsed Disease Endocervical adenocarcinoma [ICD-11: 2C77]
Responsed Drug Gallic acid Investigative
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Necroptosis hsa04217
Cell Process Cell ferroptosis
Cell apoptosis
Cell necroptosis
In Vitro Model HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
SH-SY5Y cells Neuroblastoma Homo sapiens CVCL_0019
NCI-H446 cells Lung small cell carcinoma Homo sapiens CVCL_1562
Response regulation Gallic acid (GA) could induce coexistence of multiple types of cell death pathways, including apoptosis characterized by mitochondrial cytochromecrelease and caspase-3 activation, ferroptosis characterized by lipid peroxidation, and necroptosis characterized by the loss of plasma membrane integrity in endocervical adenocarcinoma condition.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [10]
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator M-phase inducer phosphatase 1 (CDC25A) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
Ca Ski cells Cervical squamous cell carcinoma Homo sapiens CVCL_1100
In Vivo Model
Four-week-old male nude mice (N = 72) were purchased from SJA Laboratory Animal Co., Ltd. (Hunan, China), and raised in the standard animal facility room. Cervical cancer cells were infected with the control vector, Cdc25A, Cdc25A + sh-NC, and Cdc25A + sh-ErbB2 lentiviruses for 24 h and then unilateral subaxillary subcutaneously injected into nude mice (1 x 107 cells per mouse) to induce tumours.

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Response regulation Cdc25A suppressed autophagy-dependent ferroptosis in cervical cancer cells by upregulating ErbB2 levels through the dephosphorylation of PKM2. These studies revealed that Cdc25A/PKM2/ErbB2 pathway-regulated ferroptosis could serve as a therapeutic target in cervical cancer.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [10]
Responsed Disease Cervical cancer [ICD-11: 2C77.Z]
Responsed Regulator Receptor tyrosine-protein kinase erbB-2 (ERBB2) Suppressor
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model SiHa cells Cervical squamous cell carcinoma Homo sapiens CVCL_0032
Ca Ski cells Cervical squamous cell carcinoma Homo sapiens CVCL_1100
In Vivo Model
Four-week-old male nude mice (N = 72) were purchased from SJA Laboratory Animal Co., Ltd. (Hunan, China), and raised in the standard animal facility room. Cervical cancer cells were infected with the control vector, Cdc25A, Cdc25A + sh-NC, and Cdc25A + sh-ErbB2 lentiviruses for 24 h and then unilateral subaxillary subcutaneously injected into nude mice (1 x 107 cells per mouse) to induce tumours.

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Response regulation Cdc25A suppressed autophagy-dependent ferroptosis in cervical cancer cells by upregulating ErbB2 levels through the dephosphorylation of PKM2. These studies revealed that Cdc25A/PKM2/ErbB2 pathway-regulated ferroptosis could serve as a therapeutic target in cervical cancer.
References
Ref 1 HSPB1 as a novel regulator of ferroptotic cancer cell death. Oncogene. 2015 Nov 5;34(45):5617-25. doi: 10.1038/onc.2015.32. Epub 2015 Mar 2.
Ref 2 Mitochondrial dysfunction promotes aquaporin expression that controls hydrogen peroxide permeability and ferroptosis. Free Radic Biol Med. 2020 Dec;161:60-70. doi: 10.1016/j.freeradbiomed.2020.09.027. Epub 2020 Oct 2.
Ref 3 MiR-7-5p Is Involved in Ferroptosis Signaling and Radioresistance Thru the Generation of ROS in Radioresistant HeLa and SAS Cell Lines. Int J Mol Sci. 2021 Aug 2;22(15):8300. doi: 10.3390/ijms22158300.
Ref 4 Susceptibility of cervical cancer to dihydroartemisinin-induced ferritinophagy-dependent ferroptosis. Front Mol Biosci. 2023 Mar 31;10:1156062. doi: 10.3389/fmolb.2023.1156062. eCollection 2023.
Ref 5 Circular RNA circACAP2 Suppresses Ferroptosis of Cervical Cancer during Malignant Progression by miR-193a-5p/GPX4. J Oncol. 2022 Jul 8;2022:5228874. doi: 10.1155/2022/5228874. eCollection 2022.
Ref 6 Oleanolic acid inhibits cervical cancer Hela cell proliferation through modulation of the ACSL4 ferroptosis signaling pathway. Biochem Biophys Res Commun. 2021 Mar 19;545:81-88. doi: 10.1016/j.bbrc.2021.01.028. Epub 2021 Feb 3.
Ref 7 Circular RNA circLMO1 Suppresses Cervical Cancer Growth and Metastasis by Triggering miR-4291/ACSL4-Mediated Ferroptosis. Front Oncol. 2022 Mar 7;12:858598. doi: 10.3389/fonc.2022.858598. eCollection 2022.
Ref 8 Circular RNA circEPSTI1 accelerates cervical cancer progression via miR-375/409-3P/515-5p-SLC7A11 axis. Aging (Albany NY). 2021 Feb 2;13(3):4663-4673. doi: 10.18632/aging.202518. Epub 2021 Feb 2.
Ref 9 Gallic Acid Triggers Iron-Dependent Cell Death with Apoptotic, Ferroptotic, and Necroptotic Features. Toxins (Basel). 2019 Aug 26;11(9):492. doi: 10.3390/toxins11090492.
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