General Information of the Molecule (ID: Mol00574)
Name
Presenilin-1 (PSEN1) ,Homo sapiens
Synonyms
PS-1; Protein S182; PS1-CTF12; AD3; PS1; PSNL1
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Molecule Type
Protein
Gene Name
PSEN1
Gene ID
5663
Location
chr14:73136418-73223691[+]
Sequence
MTELPAPLSYFQNAQMSEDNHLSNTVRSQNDNRERQEHNDRRSLGHPEPLSNGRPQGNSR
QVVEQDEEEDEELTLKYGAKHVIMLFVPVTLCMVVVVATIKSVSFYTRKDGQLIYTPFTE
DTETVGQRALHSILNAAIMISVIVVMTILLVVLYKYRCYKVIHAWLIISSLLLLFFFSFI
YLGEVFKTYNVAVDYITVALLIWNFGVVGMISIHWKGPLRLQQAYLIMISALMALVFIKY
LPEWTAWLILAVISVYDLVAVLCPKGPLRMLVETAQERNETLFPALIYSSTMVWLVNMAE
GDPEAQRRVSKNSKYNAESTERESQDTVAENDDGGFSEEWEAQRDSHLGPHRSTPESRAA
VQELSSSILAGEDPEERGVKLGLGDFIFYSVLVGKASATASGDWNTTIACFVAILIGLCL
TLLLLAIFKKALPALPISITFGLVFYFATDYLVQPFMDQLAFHQFYI
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Function
Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels. Stimulates cell-cell adhesion via its interaction with CDH1; this stabilizes the complexes between CDH1 (E-cadherin) and its interaction partners CTNNB1 (beta-catenin), CTNND1 and JUP (gamma-catenin). Under conditions of apoptosis or calcium influx, cleaves CDH1. This promotes the disassembly of the complexes between CDH1 and CTNND1, JUP and CTNNB1, increases the pool of cytoplasmic CTNNB1, and thereby negatively regulates Wnt signaling. Required for normal embryonic brain and skeleton development, and for normal angiogenesis. Mediates the proteolytic cleavage of EphB2/CTF1 into EphB2/CTF2. The holoprotein functions as a calcium-leak channel that allows the passive movement of calcium from endoplasmic reticulum to cytosol and is therefore involved in calcium homeostasis. Involved in the regulation of neurite outgrowth. Is a regulator of presynaptic facilitation, spike transmission and synaptic vesicles replenishment in a process that depends on gamma-secretase activity. It acts through the control of SYT7 presynaptic expression.
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Uniprot ID
PSN1_HUMAN
Ensembl ID
ENSG00000080815
HGNC ID
HGNC:9508
        Click to Show/Hide the Complete Species Lineage
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Type(s) of Resistant Mechanism of This Molecule
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
8 drug(s) in total
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Cisplatin
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Bladder cancer [1]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
Sensitive Drug Cisplatin
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
DNA damage response signaling pathway Activation hsa04218
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the Gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.
Docetaxel
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Esophageal cancer [2]
Resistant Disease Esophageal cancer [ICD-11: 2B70.1]
Resistant Drug Docetaxel
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model KYSE150 cells Esophagus Homo sapiens (Human) CVCL_1348
KYSE510 cells Esophagus Homo sapiens (Human) CVCL_1354
kYSE410 cells Esophagus Homo sapiens (Human) CVCL_1352
kYSE450 cells Esophagus Homo sapiens (Human) CVCL_1353
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1.
Doxorubicin
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Bladder cancer [1]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
Sensitive Drug Doxorubicin
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
DNA damage response signaling pathway Activation hsa04218
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the Gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.
Epirubicin
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Bladder cancer [1]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
Sensitive Drug Epirubicin
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
DNA damage response signaling pathway Activation hsa04218
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the Gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.
Fluorouracil
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Esophageal cancer [2]
Resistant Disease Esophageal cancer [ICD-11: 2B70.1]
Resistant Drug Fluorouracil
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model KYSE150 cells Esophagus Homo sapiens (Human) CVCL_1348
KYSE510 cells Esophagus Homo sapiens (Human) CVCL_1354
kYSE410 cells Esophagus Homo sapiens (Human) CVCL_1352
kYSE450 cells Esophagus Homo sapiens (Human) CVCL_1353
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1.
Paclitaxel
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Esophageal cancer [2]
Resistant Disease Esophageal cancer [ICD-11: 2B70.1]
Resistant Drug Paclitaxel
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model KYSE150 cells Esophagus Homo sapiens (Human) CVCL_1348
KYSE510 cells Esophagus Homo sapiens (Human) CVCL_1354
kYSE410 cells Esophagus Homo sapiens (Human) CVCL_1352
kYSE450 cells Esophagus Homo sapiens (Human) CVCL_1353
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Bladder cancer [1]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
Sensitive Drug Paclitaxel
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
DNA damage response signaling pathway Activation hsa04218
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the Gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.
Pirarubicin
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Bladder cancer [1]
Sensitive Disease Bladder cancer [ICD-11: 2C94.0]
Sensitive Drug Pirarubicin
Molecule Alteration Expression
Up-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
DNA damage response signaling pathway Activation hsa04218
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
H-bc cells Bladder Homo sapiens (Human) CVCL_BT00
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Among the differentially expressed genes between the chemosensitive (5637) and chemoresistant (H-bc) bladder cancer cell lines, the expression level of the PSEN1 gene (presenilin 1), a key component of the Gamma-secretase, is negatively correlated with chemoresistance. A small interfering RNA mediated repression of the PSEN1 gene suppresses cell apoptosis and de-sensitizes 5637 cells, while overexpression of the presenilin 1 sensitizes H-bc cells to the drug-triggered cell death. As a direct target of microRNA-193a-3p that promotes the multi-chemoresistance of the bladder cancer cell, PSEN1 acts as an important executor for the microRNA-193a-3p's positive impact on the multi-chemoresistance of bladder cancer, probably via its activating effect on DNA damage response pathway. In addition to the mechanistic insights, the key players in this microRNA-193a-3p/PSEN1 axis are likely the diagnostic and/or therapeutic targets for an effective chemotherapy of bladder cancer.
Vinorelbine
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Disease Class: Esophageal cancer [2]
Resistant Disease Esophageal cancer [ICD-11: 2B70.1]
Resistant Drug Vinorelbine
Molecule Alteration Expression
Down-regulation
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model KYSE150 cells Esophagus Homo sapiens (Human) CVCL_1348
KYSE510 cells Esophagus Homo sapiens (Human) CVCL_1354
kYSE410 cells Esophagus Homo sapiens (Human) CVCL_1352
kYSE450 cells Esophagus Homo sapiens (Human) CVCL_1353
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Over-expression of miR-193a-3p increased the radioresistance and chemoresistance of oesophageal squamous cell carcinoma (ESCC) cells. In contrast, the down-regulation of miR-193a-3p decreased the radioresistance and chemoresistance of ESCC cells. In addition, miR-193a-3p inducing DNA damage has also been demonstrated through measuring the level of gamma-H2AX associated with miR-193a-3p. Moreover, a small interfering RNA(siRNA)-induced repression of the PSEN1 gene had an effect similar to that of miR-193a-3p up-regulation. The above processes also inhibited oesophageal cancer cells apoptosis. These findings suggest that miR-193a-3p contributes to the radiation and chemotherapy resistance of oesophageal carcinoma by down-regulating PSEN1.
Disease- and Tissue-specific Abundances of This Molecule
ICD Disease Classification 02
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Esophageal cancer [ICD-11: 2B70]
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Differential expression of molecule in resistant diseases
The Studied Tissue Esophagus
The Specified Disease Esophageal cancer
The Expression Level of Disease Section Compare with the Adjacent Tissue p-value: 1.49E-02; Fold-change: -6.23E-01; Z-score: -2.14E+00
Molecule expression in the normal tissue adjacent to the diseased tissue of patients
Molecule expression in the diseased tissue of patients
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Bladder cancer [ICD-11: 2C94]
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Differential expression of molecule in resistant diseases
The Studied Tissue Bladder tissue
The Specified Disease Bladder cancer
The Expression Level of Disease Section Compare with the Healthy Individual Tissue p-value: 7.61E-01; Fold-change: -1.93E-01; Z-score: -6.14E-01
Molecule expression in the diseased tissue of patients
Molecule expression in the normal tissue of healthy individuals
Disease-specific Molecule Abundances Click to View the Clearer Original Diagram
Tissue-specific Molecule Abundances in Healthy Individuals
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References
Ref 1 The miR-193a-3p regulated PSEN1 gene suppresses the multi-chemoresistance of bladder cancer. Biochim Biophys Acta. 2015 Mar;1852(3):520-8. doi: 10.1016/j.bbadis.2014.12.014. Epub 2014 Dec 24.
Ref 2 miR-193a-3p regulation of chemoradiation resistance in oesophageal cancer cells via the PSEN1 gene. Gene. 2016 Apr 1;579(2):139-45. doi: 10.1016/j.gene.2015.12.060. Epub 2015 Dec 29.

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