General Information of the Disease (ID: DIS00046)
Name
Bladder cancer
ICD
ICD-11: 2C94
Full List of Target(s) of This Ferroptosis-centered Disease
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Bladder cancer [ICD-11: 2C94]
Responsed Drug FIN56 Investigative
Pathway Response Fatty acid metabolism hsa01212
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model J82 cells Bladder carcinoma Homo sapiens CVCL_0359
253J cells Bladder carcinoma Homo sapiens CVCL_7935
T24 cells Bladder carcinoma Homo sapiens CVCL_0554
RT-112 cells Bladder carcinoma Homo sapiens CVCL_1670
mEFs (Mouse embryonic fibroblasts)
Response regulation Fin56, a type 3 inducer, leads to ferroptosis mainly by promoting GPX4 degradation. Fin56 induces ferroptosis and autophagy in bladder cancer cells and that Fin56-triggered ferroptosis mechanistically depends on the autophagic machinery.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [2]
Target for Ferroptosis Suppressor
Responsed Disease Bladder cancer [ICD-11: 2C94]
Responsed Drug Quinazolinyl-arylurea derivatives 7J Investigative
Pathway Response Ferroptosis hsa04216
Apoptosis hsa04210
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell apoptosis
Cell autophagy
Cell proliferation
In Vitro Model BEL-7402 cells Endocervical adenocarcinoma Homo sapiens CVCL_5492
MGC-803 cells Gastric mucinous adenocarcinoma Homo sapiens CVCL_5334
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
HCC827 cells Lung adenocarcinoma Homo sapiens CVCL_2063
T24 cells Bladder carcinoma Homo sapiens CVCL_0554
RT4 cells Bladder carcinoma Homo sapiens CVCL_0036
Response regulation Compound 7j treatment could trigger three different cell death forms including apoptosis, ferroptosis, and autophagy; which form would occur depended on the concentrations and incubation time of 7j. Ferroptosis and autophagy occurred in the case of higher concentrations combining with extended incubation time through effectively regulating the Sxc-/GPx4/ROS and PI3K/Akt/mTOR/ULK1 pathways, respectively. Compound 7j could be a promising lead for molecular-targeted anti- bladder cancer agents' discovery.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [3]
Target for Ferroptosis Suppressor
Responsed Disease Bladder cancer [ICD-11: 2C94]
Responsed Regulator 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) Suppressor
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model T24 cells Bladder carcinoma Homo sapiens CVCL_0554
5637 cells Bladder carcinoma Homo sapiens CVCL_0126
J82 cells Bladder carcinoma Homo sapiens CVCL_0359
UM-UC-3 cells Bladder carcinoma Homo sapiens CVCL_1783
In Vivo Model
Twenty female BALB/c nude mice (4-6-weeks old, 15 g) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China). All mice were housed under specific pathogen-free conditions in 12/12 cycle of light at room temperature (24-26 ). Mice were fed a full fat diet and autoclaved water. The number of mice did not exceed five per cage. A total of 1 x 107 infected 5637 cells were suspended in 100 uL PBS and injected into the shoulder of the mice. Tumor length (L) and width (W) were observed for 4 weeks. Tumor volume (V) was monitored by measuring the length and width of the tumor using the following equation: V = (L x W2) x 0.5. The mice were euthanized by cervical dislocation after inhalational of CO2 when the maximum diameter of any tumor was near 1.5 cm. Tumor tissues were excised and embedded in paraffin for ematoxylin and eosin (HE) or IHC staining.

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Response regulation PSMD14 is highly expressed in bladder cancer tissues, and that PSMD14 expression correlated with poor disease-free survival. Depletion of PSMD14 could inhibit the proliferation and induce ferroptosis of bladder cancer cells through the downregulation of GPX4.
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [4]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Bladder cancer [ICD-11: 2C94]
Responsed Drug Erianin Investigative
Pathway Response Fatty acid metabolism hsa01212
Glutathione metabolism hsa00480
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model RT4 cells Bladder carcinoma Homo sapiens CVCL_0036
KU-19-19 cells Bladder carcinoma Homo sapiens CVCL_1344
In Vivo Model
4-weeks-old female BALB/c nude mice aged were injected into 5 x 105 cells. Every 2 days mice weight and tumor size were assessed, and the tumor volume (V) was calculated with the formula: (maximum length) x (maximum width)2/2. Once tumors were found, the mice were stochastically divided into 2 groups: the control (PBS) group and the treatment (erianin 100 mg/kg) group. For 14 days, mice were injected intraperitoneally with drugs once a day, then puting the mice to death, after that tumors were taken for IHC (immunohistochemical) analysis.

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Response regulation Erianin inhibited cell proliferation and triggered cell death in bladder cancer cells. Mechanistically, we showed NRF2 was a key determinant for erianin-triggered ferroptosis. NRF2 activation by TBHQ treatment protected against erianin-induced cell death and increased the expression of GPX4, ferritin, xCT and glutaminase.
Heat shock protein beta-1 (HSPB1)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [5]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Bladder cancer [ICD-11: 2C94]
Responsed Regulator CircST6GALNAC6 (circRNA) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model UM-UC-3 cells Bladder carcinoma Homo sapiens CVCL_1783
J82 cells Bladder carcinoma Homo sapiens CVCL_0359
Response regulation CircST6GALNAC6 inhibits HSPB1 and promotes cell ferroptosis by occupying the phosphorylation site (Ser-15) of HSBP1 and activating the P38 MAPK signaling pathway. Therefore, enhancing the expression of circST6GALNAC6 to promote ferroptosis or using circST6GALNAC6 as a biomarker of ferroptosis sensitivity is of considerable importance to the development and application of ferroptosis intervention methods in bladder cancer.
Ferritin heavy chain (FTH1)
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [6]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Bladder cancer [ICD-11: 2C94]
Responsed Drug Baicalin Terminated
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model 5637 cells Bladder carcinoma Homo sapiens CVCL_0126
BLSC-KU-19 cells Leukemia Bos taurus CVCL_VN09
In Vivo Model
All mouse experiments were approved by the Use and Care of Animals Committee at Hangzhou Normal University. About 6 x 106 KU-19-19cells were injected into the about 3-5 weeks old female BALB/c nude mice (about 18 g,n = 5).Once palpable tumors appeared, the mice were randomized in four groups: the control (deionized water containing 7% Tween 80 and 0.1% CMC-Na) group, the DFO (100 mg/kg/day) group, the baicalin (200 mg/kg/day) group, and DFO + baicalin group. After 10 days of drug administration (intraperitoneal injection, once daily), mice were sacrificed, and tumor specimens resected were collected for immunohistochemical staining and Perl's staining (Solarbio Life Sciences, G1420).

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Response regulation Baicalin triggered ferroptosis in vitro and in vivo, as evidenced by ROS accumulation and intracellular chelate iron enrichment. Baicalin exerts its anticancer activity in bladder cancer by inducing FTH1-dependent ferroptosis, which will hopefully provide great therapeutic potential for bladder cancer treatment.
Unspecific Target
In total 3 item(s) under this target
Experiment 1 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Responsed Disease Bladder cancer [ICD-11: 2C94]
Responsed Regulator RP11-89 (IncRNA) Suppressor
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell invasion
In Vitro Model 5637 cells Bladder carcinoma Homo sapiens CVCL_0126
T24 cells Bladder carcinoma Homo sapiens CVCL_0554
SV-HUC-1 cells Normal Homo sapiens CVCL_3798
In Vivo Model
The male nude mice (BALB/c, aged 4-6 weeks, 18-20 g) were randomly divided into four groups (Sample size: 5-7 mice per group) and inoculated with cells as follows: sh-RP11-89 stable transfected 5637 Cell (1 x 107 cells); shNC-RP11-89 stable transfected 5637 Cell (1 x 107 cells); sh-RP11-89 stable transfected 5637 Cell + antagomiR-129-5p (1 x 107 cells; 10 nmol antagomiR-129-5p injection/mouse, 3 days after tumor formation); and sh-RP11-89 stable transfected 5637 Cell + miR-129-5p NC group (1 x 107 cells; 10 nmol miR-129-5p NC injection/mouse, 3 days after tumor formation). Cells were mixed with matrigel (1:2) and inoculated subcutaneously at the right rear back region.

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Response regulation RP11-89 "sponges" miR-129-5p and upregulates PROM2. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.
Experiment 2 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Responsed Disease Bladder cancer [ICD-11: 2C94]
Responsed Regulator hsa-miR-129-5p (miRNA) Driver
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell invasion
In Vitro Model 5637 cells Bladder carcinoma Homo sapiens CVCL_0126
T24 cells Bladder carcinoma Homo sapiens CVCL_0554
SV-HUC-1 cells Normal Homo sapiens CVCL_3798
In Vivo Model
The male nude mice (BALB/c, aged 4-6 weeks, 18-20 g) were randomly divided into four groups (Sample size: 5-7 mice per group) and inoculated with cells as follows: sh-RP11-89 stable transfected 5637 Cell (1 x 107 cells); shNC-RP11-89 stable transfected 5637 Cell (1 x 107 cells); sh-RP11-89 stable transfected 5637 Cell + antagomiR-129-5p (1 x 107 cells; 10 nmol antagomiR-129-5p injection/mouse, 3 days after tumor formation); and sh-RP11-89 stable transfected 5637 Cell + miR-129-5p NC group (1 x 107 cells; 10 nmol miR-129-5p NC injection/mouse, 3 days after tumor formation). Cells were mixed with matrigel (1:2) and inoculated subcutaneously at the right rear back region.

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Response regulation RP11-89 "sponges" miR-129-5p and upregulates PROM2. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.
Experiment 3 Reporting the Ferroptosis-centered Disease Response by This Target [7]
Responsed Disease Bladder cancer [ICD-11: 2C94]
Responsed Regulator Prominin-2 (PROM2) Suppressor
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
Cell invasion
In Vitro Model 5637 cells Bladder carcinoma Homo sapiens CVCL_0126
T24 cells Bladder carcinoma Homo sapiens CVCL_0554
SV-HUC-1 cells Normal Homo sapiens CVCL_3798
In Vivo Model
The male nude mice (BALB/c, aged 4-6 weeks, 18-20 g) were randomly divided into four groups (Sample size: 5-7 mice per group) and inoculated with cells as follows: sh-RP11-89 stable transfected 5637 Cell (1 x 107 cells); shNC-RP11-89 stable transfected 5637 Cell (1 x 107 cells); sh-RP11-89 stable transfected 5637 Cell + antagomiR-129-5p (1 x 107 cells; 10 nmol antagomiR-129-5p injection/mouse, 3 days after tumor formation); and sh-RP11-89 stable transfected 5637 Cell + miR-129-5p NC group (1 x 107 cells; 10 nmol miR-129-5p NC injection/mouse, 3 days after tumor formation). Cells were mixed with matrigel (1:2) and inoculated subcutaneously at the right rear back region.

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Response regulation RP11-89 "sponges" miR-129-5p and upregulates PROM2. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.
References
Ref 1 Fin56-induced ferroptosis is supported by autophagy-mediated GPX4 degradation and functions synergistically with mTOR inhibition to kill bladder cancer cells. Cell Death Dis. 2021 Oct 29;12(11):1028. doi: 10.1038/s41419-021-04306-2.
Ref 2 Synthesis and invitro anti-bladder cancer activity evaluation of quinazolinyl-arylurea derivatives. Eur J Med Chem. 2020 Nov 1;205:112661. doi: 10.1016/j.ejmech.2020.112661. Epub 2020 Jul 24.
Ref 3 Depletion of PSMD14 suppresses bladder cancer proliferation by regulating GPX4. PeerJ. 2023 Jan 6;11:e14654. doi: 10.7717/peerj.14654. eCollection 2023.
Ref 4 Natural Product Erianin Inhibits Bladder Cancer Cell Growth by Inducing Ferroptosis via NRF2 Inactivation. Front Pharmacol. 2021 Oct 29;12:775506. doi: 10.3389/fphar.2021.775506. eCollection 2021.
Ref 5 CircRNA-ST6GALNAC6 increases the sensitivity of bladder cancer cells to erastin-induced ferroptosis by regulating the HSPB1/P38 axis. Lab Invest. 2022 Dec;102(12):1323-1334. doi: 10.1038/s41374-022-00826-3. Epub 2022 Aug 9.
Ref 6 Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1. Acta Pharm Sin B. 2021 Dec;11(12):4045-4054. doi: 10.1016/j.apsb.2021.03.036. Epub 2021 Mar 27.
Ref 7 LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer. Cell Death Dis. 2021 Nov 2;12(11):1043. doi: 10.1038/s41419-021-04296-1.