Ferroptosis-centered Disease Response Information
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.
Click to Show/Hide
|
||||
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.
Click to Show/Hide
|
||||
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).
Click to Show/Hide
|
||||
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.
Click to Show/Hide
|
||||
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.
Click to Show/Hide
|
||||
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.
Click to Show/Hide
|
||||
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