Molecule Information

General Information of the Molecule (ID: Mol00248)

• Name: Bcl-2 homologous antagonist/killer (BAK1) ,Homo sapiens
• Synonyms: Apoptosis regulator BAK; Bcl-2-like protein 7; Bcl2-L-7; BAK; BCL2L7; CDN1
• Molecule Type: Protein
• Gene Name: BAK1
• Gene ID: 578
• Location: chr6:33572547-33580293[-]
• Sequence:
  MASGQGPGPPRQECGEPALPSASEEQVAQDTEEVFRSYVFYRHQQEQEAEGVAAPADPEM
  VTLPLQPSSTMGQVGRQLAIIGDDINRRYDSEFQTMLQHLQPTAENAYEYFTKIATSLFE
  SGINWGRVVALLGFGYRLALHVYQHGLTGFLGQVTRFVVDFMLHHCIARWIAQRGGWVAA
  LNLGNGPILNVLVVLGVVLLGQFVVRRFFKS
• Function: Plays a role in the mitochondrial apoptosic process. Upon arrival of cell death signals, promotes mitochondrial outer membrane (MOM) permeabilization by oligomerizing to form pores within the MOM. This releases apoptogenic factors into the cytosol, including cytochrome c, promoting the activation of caspase 9 which in turn processes and activates the effector caspases.
• Uniprot ID: BAK_HUMAN
• Ensembl ID: ENSG00000030110
• HGNC ID: HGNC:949

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) 5 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Ovarian cancer [1]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: OV2008 cells; Ovary; Homo sapiens (Human); CVCL_0473
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: Bak1 was a direct target of miR-125b, and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin. miR-125b has a sig-nificantly promoting effect on chemoresistance of C13* cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression.

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Primitive neuroectodermal tumor [2]

• Resistant Disease: Primitive neuroectodermal tumor [ICD-11: 2A00.08]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR125b-p53/BAKT signaling pathway; Activation; hsa05206
• In Vitro Model: RD-ES cells; Bones; Homo sapiens (Human); CVCL_2169
• In Vitro Model: Sk-ES cells; Bones; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: VH-64 cells; Bones; Homo sapiens (Human); CVCL_9672
• In Vitro Model: WE-68 cells; Bones; Homo sapiens (Human); CVCL_9717
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Celltiter-glo luminescent cell viability assay
• Mechanism Description: miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.

Disease Class: Acute promyelocytic leukemia [3]

• Resistant Disease: Acute promyelocytic leukemia [ICD-11: 2A60.2]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• In Vitro Model: NB4 cells; Bone marrow; Homo sapiens (Human); CVCL_0005
• In Vivo Model: BALB/c nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: CCK8 assay
• Mechanism Description: miR-125b could promote leukemic cell proliferation and inhibit cell apoptosis by regulating the expression of tumor suppressor BCL2-antagonist/killer 1 (Bak1). transfection of a miR-125b duplex into AML cells can increase their resistance to therapeutic drugs.

Etoposide

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Primitive neuroectodermal tumor [2]

• Resistant Disease: Primitive neuroectodermal tumor [ICD-11: 2A00.08]
• Resistant Drug: Etoposide
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR125b-p53/BAKT signaling pathway; Activation; hsa05206
• In Vitro Model: RD-ES cells; Bones; Homo sapiens (Human); CVCL_2169
• In Vitro Model: Sk-ES cells; Bones; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: VH-64 cells; Bones; Homo sapiens (Human); CVCL_9672
• In Vitro Model: WE-68 cells; Bones; Homo sapiens (Human); CVCL_9717
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Celltiter-glo luminescent cell viability assay
• Mechanism Description: miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.

Paclitaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Breast cancer [4]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Resistant Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• In Vitro Model: BT474 cells; Breast; Homo sapiens (Human); CVCL_0179
• In Vitro Model: MDA-MB-436 cells; Breast; Homo sapiens (Human); CVCL_0623
• In Vitro Model: MDA-MB-435 cells; Breast; Homo sapiens (Human); CVCL_0417
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Celltiter 96 aqueous one solution cell proliferation assay
• Mechanism Description: miR-125b was up-regulated in Taxol-resistant cells, causing a marked inhibition of Taxol-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to Taxol in cancer cells. The pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) is a direct target of miR-125b. Down-regulation of Bak1 suppressed Taxol-induced apoptosis and led to an increased resistance to Taxol.

Vincristine

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Primitive neuroectodermal tumor [2]

• Resistant Disease: Primitive neuroectodermal tumor [ICD-11: 2A00.08]
• Resistant Drug: Vincristine
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: miR125b-p53/BAKT signaling pathway; Activation; hsa05206
• In Vitro Model: RD-ES cells; Bones; Homo sapiens (Human); CVCL_2169
• In Vitro Model: Sk-ES cells; Bones; Homo sapiens (Human); CVCL_0627
• In Vitro Model: Sk-N-MC cells; Bones; Homo sapiens (Human); CVCL_0530
• In Vitro Model: TC-71 cells; Bones; Homo sapiens (Human); CVCL_2213
• In Vitro Model: VH-64 cells; Bones; Homo sapiens (Human); CVCL_9672
• In Vitro Model: WE-68 cells; Bones; Homo sapiens (Human); CVCL_9717
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: Celltiter-glo luminescent cell viability assay
• Mechanism Description: miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.62E-38; Fold-change: 2.48E-01; Z-score: 9.37E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.54E-01; Fold-change: -2.48E-01; Z-score: -6.09E-01
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.96E-01; Fold-change: 2.73E-01; Z-score: 4.14E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.91E-02; Fold-change: 1.52E-01; Z-score: 5.09E-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: 2.79E-76; Fold-change: 4.57E-01; Z-score: 1.58E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 6.81E-04; Fold-change: 1.48E-01; Z-score: 3.92E-01

Ovarian cancer [ICD-11: 2C73]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Ovary
• The Specified Disease: Ovarian cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.14E-05; Fold-change: 8.84E-01; Z-score: 2.67E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.10E-03; Fold-change: 6.93E-01; Z-score: 1.13E+00

References

• Ref 1: miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1. J Huazhong Univ Sci Technolog Med Sci. 2011 Aug;31(4):543. doi: 10.1007/s11596-011-0487-z. Epub 2011 Aug 7.
• Ref 2: miR-125b develops chemoresistance in Ewing sarcoma/primitive neuroectodermal tumor. Cancer Cell Int. 2013 Mar 4;13(1):21. doi: 10.1186/1475-2867-13-21.
• Ref 3: Upregulation of microRNA-125b contributes to leukemogenesis and increases drug resistance in pediatric acute promyelocytic leukemia. Mol Cancer. 2011 Sep 1;10:108. doi: 10.1186/1476-4598-10-108.
• Ref 4: MicroRNA-125b confers the resistance of breast cancer cells to paclitaxel through suppression of pro-apoptotic Bcl-2 antagonist killer 1 (Bak1) expression. J Biol Chem. 2010 Jul 9;285(28):21496-507. doi: 10.1074/jbc.M109.083337. Epub 2010 May 11.