Molecule Information
General Information of the Molecule (ID: Mol04076)
| Name |
Transforming growth factor beta 1 (TGFB1)
,Homo sapiens
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| Molecule Type |
Protein
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| Gene Name |
TGFB1
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| Gene ID | |||||
| Location |
chr19:41301587-41353922[-]
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| Sequence |
MPPSGLRLLPLLLPLLWLLVLTPGRPAAGLSTCKTIDMELVKRKRIEAIRGQILSKLRLA
SPPSQGEVPPGPLPEAVLALYNSTRDRVAGESAEPEPEPEADYYAKEVTRVLMVETHNEI YDKFKQSTHSIYMFFNTSELREAVPEPVLLSRAELRLLRLKLKVEQHVELYQKYSNNSWR YLSNRLLAPSDSPEWLSFDVTGVVRQWLSRGGEIEGFRLSAHCSCDSRDNTLQVDINGFT TGRRGDLATIHGMNRPFLLLMATPLERAQHLQSSRHRRALDTNYCFSSTEKNCCVRQLYI DFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLALYNQHNPGASAAPCCVPQA LEPLPIVYYVGRKPKVEQLSNMIVRSCKCS Click to Show/Hide
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| 3D-structure |
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| Function |
Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively. .; [Latency-associated peptide]: Required to maintain the Transforming growth factor beta-1 (TGF-beta-1) chain in a latent state during storage in extracellular matrix (PubMed:28117447). Associates non-covalently with TGF-beta-1 and regulates its activation via interaction with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS, that control activation of TGF-beta-1 (PubMed:19651619, PubMed:19750484, PubMed:2022183, PubMed:22278742, PubMed:8617200, PubMed:8939931). Interaction with LRRC33/NRROS regulates activation of TGF-beta-1 in macrophages and microglia (Probable). Interaction with LRRC32/GARP controls activation of TGF-beta-1 on the surface of activated regulatory T-cells (Tregs) (PubMed:19651619, PubMed:19750484, PubMed:22278742). Interaction with integrins (ITGAV:ITGB6 or ITGAV:ITGB8) results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). .; [Transforming growth factor beta-1]: Multifunctional protein that regulates the growth and differentiation of various cell types and is involved in various processes, such as normal development, immune function, microglia function and responses to neurodegeneration (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency- associated peptide (LAP) and Transforming growth factor beta-1 (TGF- beta-1) chains remain non-covalently linked rendering TGF-beta-1 inactive during storage in extracellular matrix (PubMed:29109152). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1, LRRC32/GARP and LRRC33/NRROS that control activation of TGF- beta-1 and maintain it in a latent state during storage in extracellular milieus (PubMed:19651619, PubMed:19750484, PubMed:2022183, PubMed:22278742, PubMed:8617200, PubMed:8939931). TGF- beta-1 is released from LAP by integrins (ITGAV:ITGB6 or ITGAV:ITGB8): integrin-binding to LAP stabilizes an alternative conformation of the LAP bowtie tail and results in distortion of the LAP chain and subsequent release of the active TGF-beta-1 (PubMed:22278742, PubMed:28117447). Once activated following release of LAP, TGF-beta-1 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (PubMed:20207738). While expressed by many cells types, TGF-beta-1 only has a very localized range of action within cell environment thanks to fine regulation of its activation by Latency- associated peptide chain (LAP) and 'milieu molecules' (By similarity). Plays an important role in bone remodeling: acts as a potent stimulator of osteoblastic bone formation, causing chemotaxis, proliferation and differentiation in committed osteoblasts (By similarity). Can promote either T-helper 17 cells (Th17) or regulatory T-cells (Treg) lineage differentiation in a concentration-dependent manner (By similarity). At high concentrations, leads to FOXP3-mediated suppression of RORC and down-regulation of IL-17 expression, favoring Treg cell development (By similarity). At low concentrations in concert with IL-6 and IL-21, leads to expression of the IL-17 and IL-23 receptors, favoring differentiation to Th17 cells (By similarity). Stimulates sustained production of collagen through the activation of CREB3L1 by regulated intramembrane proteolysis (RIP) (PubMed:25310401). Mediates SMAD2/3 activation by inducing its phosphorylation and subsequent translocation to the nucleus (PubMed:25893292, PubMed:29483653, PubMed:30696809). Positively regulates odontoblastic differentiation in dental papilla cells, via promotion of IPO7-mediated translocation of phosphorylated SMAD2 to the nucleus and subsequent transcription of target genes (By similarity). Can induce epithelial-to-mesenchymal transition (EMT) and cell migration in various cell types (PubMed:25893292, PubMed:30696809). .
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| Uniprot ID | |||||
| Ensembl ID | |||||
| HGNC ID | |||||
| Click to Show/Hide the Complete Species Lineage | |||||
Type(s) of Resistant Mechanism of This Molecule
MRAP: Metabolic Reprogramming via Altered Pathways
Drug Resistance Data Categorized by Drug
Investigative Drug(s)
1 drug(s) in total
Anthracyclines
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
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Metabolic Reprogramming via Altered Pathways (MRAP)
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| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Anthracyclines | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | K562/ADR cells | Blood | Homo sapiens (Human) | CVCL_0004 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX8 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Anthracyclines | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | HL60/ADR cells | Blood | Homo sapiens (Human) | CVCL_0002 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX7 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Anthracyclines | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | K562 cells | Blood | Homo sapiens (Human) | CVCL_0004 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX6 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Anthracyclines | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | HL-60 cells | Peripheral blood | Homo sapiens (Human) | CVCL_0002 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX5 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Anthracyclines | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
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| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | KG-1 A cells | Blood | Homo sapiens (Human) | CVCL_0374 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX4 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Anthracyclines | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
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| Experimental Note | Identified from the Human Clinical Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vivo Model | HCC patients | Homo Sapiens | ||
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
Approved Drug(s)
1 drug(s) in total
Cytarabine
| Drug Resistance Data Categorized by Their Corresponding Mechanisms | ||||
|
Metabolic Reprogramming via Altered Pathways (MRAP)
|
||||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Cytarabine | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
|||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | KG-1 A cells | Blood | Homo sapiens (Human) | CVCL_0374 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX9 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Cytarabine | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
|||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | K562/ADR cells | Blood | Homo sapiens (Human) | CVCL_0004 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX13 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Cytarabine | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
|||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | HL60/ADR cells | Blood | Homo sapiens (Human) | CVCL_0002 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX12 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Cytarabine | |||
| Molecule Alteration | Expression | Up-regulation |
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| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
|||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | K562 cells | Blood | Homo sapiens (Human) | CVCL_0004 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX11 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Cytarabine | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
|||
| Experimental Note | Revealed Based on the Cell Line Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vitro Model | HL-60 cells | Peripheral blood | Homo sapiens (Human) | CVCL_0002 |
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
| Experiment for Drug Resistance |
CCK8 assay | |||
| Mechanism Description | In this study, we find that TGFB1 levels are elevated in relapsed or refractory AML patients and in drug-resistant cell lines, and can induce chemoresistance by stimulating the activation of the TGFB signaling pathway via an autocrine/paracrine manner. This process may be achieved through metabolic reprogramming induced by TGFB1-triggered SOX10 expression. | |||
| Disease Class: Acute myeloid leukemia [ICD-11: 2A60.0] | [1] | |||
| Metabolic Type | Lipid metabolism | |||
| Resistant Disease | Acute myeloid leukemia [ICD-11: 2A60.0] | |||
| Resistant Drug | Cytarabine | |||
| Molecule Alteration | Expression | Up-regulation |
||
| Differential expression of the molecule in resistant disease | ||||
| Classification of Disease | Acute myeloid leukemia [ICD-11: 2A60] | |||
| The Specified Disease | Acute myeloid leukemia | |||
| The Studied Tissue | Blood | |||
| The Expression Level of Disease Section Compare with the Healthy Individual Tissue | p-value: 1.40E-07 Fold-change: 6.20E-01 Z-score: 6.08E+00 |
|||
| Experimental Note | Identified from the Human Clinical Data | |||
| Cell Pathway Regulation | TGF-beta signaling pathway | Activation | hsa04350 | |
| In Vivo Model | HCC patients | Homo Sapiens | ||
| Experiment for Molecule Alteration |
qRT-PCR; Western blot analysis | |||
References
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