Molecule Information

General Information of the Molecule (ID: Mol00037)

• Name: Caspase-9 (CASP9) ,Homo sapiens
• Synonyms: CASP-9; Apoptotic protease Mch-6; Apoptotic protease-activating factor 3; APAF-3; ICE-like apoptotic protease 6; ICE-LAP6; MCH6
• Molecule Type: Protein
• Gene Name: CASP9
• Gene ID: 842
• Location: chr1:15490832-15526534[-]
• Sequence:
  MDEADRRLLRRCRLRLVEELQVDQLWDALLSRELFRPHMIEDIQRAGSGSRRDQARQLII
  DLETRGSQALPLFISCLEDTGQDMLASFLRTNRQAAKLSKPTLENLTPVVLRPEIRKPEV
  LRPETPRPVDIGSGGFGDVGALESLRGNADLAYILSMEPCGHCLIINNVNFCRESGLRTR
  TGSNIDCEKLRRRFSSLHFMVEVKGDLTAKKMVLALLELAQQDHGALDCCVVVILSHGCQ
  ASHLQFPGAVYGTDGCPVSVEKIVNIFNGTSCPSLGGKPKLFFIQACGGEQKDHGFEVAS
  TSPEDESPGSNPEPDATPFQEGLRTFDQLDAISSLPTPSDIFVSYSTFPGFVSWRDPKSG
  SWYVETLDDIFEQWAHSEDLQSLLLRVANAVSVKGIYKQMPGCFNFLRKKLFFKTS
• Function: Involved in the activation cascade of caspases responsible for apoptosis execution. Binding of caspase-9 to Apaf-1 leads to activation of the protease which then cleaves and activates caspase-3. Promotes DNA damage-induced apoptosis in a ABL1/c-Abl-dependent manner. Proteolytically cleaves poly(ADP-ribose) polymerase (PARP).; FUNCTION: Isoform 2 lacks activity is an dominant-negative inhibitor of caspase-9.
• Uniprot ID: CASP9_HUMAN
• Ensembl ID: ENSG00000132906
• HGNC ID: HGNC:1511

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) 3 drug(s) in total

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [1]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: Sk-MES-1 cells; Lung; Homo sapiens (Human); CVCL_0630
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Down-regulation of miR-21 inhibited growth, colony formation, antiapoptotic Bcl-2 expression and promoted proapoptotic Bax and caspase-9 expression in A549 cells treated with DDP. Upregulation of miR-21 promoted growth and colony formation in Sk-MES-1 cells treated with DDP. Furthermore, downregulation of miR-21 reduced growth of implanted tumors, suggesting that miR-21 inhibition could enhance the sensitivity of A549 cells to DDP in vivo. These data suggest an appropriate combination of DDP and miR-21 regulation might be a potential approach to lung cancer therapy. Combined DDP application with miR-21 downregulation for the treatment of lung cancer would help achieve effective treatment and reduce DDP side effects.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Activation; hsa01521
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• Experiment for Molecule Alteration: Western blot analysis; TUNEL assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Long noncoding RNA LINP1 acts as an oncogene and promotes chemoresistance against 5-fluoroutacil and doxorubicin by inhibiting chemotherapeutics-induced apoptosis (apoptosis-related proteins such as caspase-8, caspase-9 and Bax proteins) in breast cancer.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [2]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• 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 Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• Cell Pathway Regulation: Epithelial mesenchymal transition signaling pathway; Activation; hsa01521
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: MDA-MB-468 cells; Breast; Homo sapiens (Human); CVCL_0419
• Experiment for Molecule Alteration: Western blot analysis; TUNEL assay
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Long noncoding RNA LINP1 acts as an oncogene and promotes chemoresistance against 5-fluoroutacil and doxorubicin by inhibiting chemotherapeutics-induced apoptosis (apoptosis-related proteins such as caspase-8, caspase-9 and Bax proteins) in breast cancer.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Lung cancer [ICD-11: 2C25]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Lung
• The Specified Disease: Lung cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.38E-01; Fold-change: -5.80E-02; Z-score: -1.77E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 4.45E-05; Fold-change: -2.06E-01; Z-score: -5.15E-01

Breast cancer [ICD-11: 2C60]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Breast tissue
• The Specified Disease: Breast cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.78E-02; Fold-change: -3.38E-02; Z-score: -9.44E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 6.74E-02; Fold-change: -9.88E-02; Z-score: -2.24E-01

References

• Ref 1: Downregulation of miR-21 increases cisplatin sensitivity of non-small-cell lung cancer. Cancer Genet. 2014 May;207(5):214-20. doi: 10.1016/j.cancergen.2014.04.003. Epub 2014 Apr 13.
• Ref 2: Long noncoding RNA LINP1 acts as an oncogene and promotes chemoresistance in breast cancer. Cancer Biol Ther. 2018 Feb 1;19(2):120-131. doi: 10.1080/15384047.2017.1394543. Epub 2018 Jan 2.