Molecule Information

General Information of the Molecule (ID: Mol00023)

• Name: Bcl-2-like protein 2 (BCL2L2) ,Homo sapiens
• Synonyms: Bcl2-L-2; Apoptosis regulator Bcl-W; BCLW; KIAA0271
• Molecule Type: Protein
• Gene Name: BCL2L2
• Gene ID: 599
• Location: chr14:23298790-23311751[+]
• Sequence:
  MATPASAPDTRALVADFVGYKLRQKGYVCGAGPGEGPAADPLHQAMRAAGDEFETRFRRT
  FSDLAAQLHVTPGSAQQRFTQVSDELFQGGPNWGRLVAFFVFGAALCAESVNKEMEPLVG
  QVQEWMVAYLETQLADWIHSSGGWAEFTALYGDGALEEARRLREGNWASVRTVLTGAVAL
  GALVTVGAFFASK
• 3D-structure: PDB ID: 1O0L; Classification: Apoptosis; Method: Solution nmr; Resolution: No Resolution Dat Å
• Function: Promotes cell survival. Blocks dexamethasone-induced apoptosis. Mediates survival of postmitotic Sertoli cells by suppressing death-promoting activity of BAX.
• Uniprot ID: B2CL2_HUMAN
• Ensembl ID: ENSG00000129473
• HGNC ID: HGNC:995

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) 6 drug(s) in total

Fluorouracil

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Hepatocellular carcinoma [ICD-11: 2C12.2] [1]

• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Sensitive Drug: Fluorouracil
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Liver cancer [ICD-11: 2C12]
• The Specified Disease: Liver cancer
• The Studied Tissue: Liver tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 9.79E-03; Fold-change: -3.17E-02; Z-score: -2.69E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: BEL-7402 cells; Liver; Homo sapiens (Human); CVCL_5492
• In Vitro Model: Bel-7402/5-Fu cells; Liver; Homo sapiens (Human); CVCL_5493
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-195 antisense oligonucleotide induced drug resistance in BEL-7402/5-FU cells. miR-195 overexpression repressed Bcl-w protein level. miR-195, one of the down-regulated miRNAs in BEL-7402/5-FU cells, was demonstrated to play a role in the development of drug resistance in hepatocellular carcinoma cells by targeting the antiapoptotic gene, Bcl-w.

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Colon cancer [ICD-11: 2B90.1] [2]

• Sensitive Disease: Colon cancer [ICD-11: 2B90.1]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Colon cancer [ICD-11: 2B90]
• The Specified Disease: Colon cancer
• The Studied Tissue: Colon tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.40E-42; Fold-change: -8.36E-02; Z-score: -1.71E+01
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: HT29 Cells; Colon; Homo sapiens (Human); CVCL_A8EZ
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Suppression of miR-195 leads to elevation of its direct target gene BCL2L2 expression therefore makes the human colon cancer cells more resistant to Dox.

Paclitaxel

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Non-small cell lung cancer [ICD-11: 2C25.Y] [3]

• Sensitive Disease: Non-small cell lung cancer [ICD-11: 2C25.Y]
• Sensitive Drug: Paclitaxel
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung cancer
• The Studied Tissue: Lung tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.83E-48; Fold-change: -1.29E-01; Z-score: -1.85E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell invasion; Inhibition; hsa05200
• Cell Pathway Regulation: Cell migration; Inhibition; hsa04670
• Cell Pathway Regulation: Cell viability; Inhibition; hsa05200
• Cell Pathway Regulation: PI3K/AKT signaling pathway; Inhibition; hsa04151
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Dual-luciferase reporter assay; qRT-PCR; Western blot analysis
• Experiment for Drug Resistance: MTT assay; Flow cytometric analysis; Caspase-3 activity assay
• Mechanism Description: Overexpression of miR107 promotes apoptosis and inhibits proliferation and mobility of A549/Taxol cells under treatment with paclitaxel in vitro. miR107/Bcl-w axis regulates paclitaxel chemoresistance through PI3k-Akt pathway, up-regulation of miR107 resensitizes paclitaxel-resistant NSCLC cells by targeting Bcl-w. Aberrant activation of PI3k-Akt pathway and genetic alterations of its components lead to tumorigenesis.

Cisplatin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Bladder cancer [ICD-11: 2C94.0] [4]

• Sensitive Disease: Bladder cancer [ICD-11: 2C94.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Bladder cancer [ICD-11: 2C94]
• The Specified Disease: Bladder cancer
• The Studied Tissue: Bladder tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.27E-03; Fold-change: -1.78E-01; Z-score: -4.91E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: HEK293T cells; Kidney; Homo sapiens (Human); CVCL_0063
• In Vitro Model: 5637 cells; Bladder; Homo sapiens (Human); CVCL_0126
• In Vitro Model: T24 cells; Bladder; Homo sapiens (Human); CVCL_0554
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR-203 could directly bind the 3'-UTR of both Bcl-w and Survivin, resulting in down-regulated expression of Bcl-w and Survivin at post-transcriptional level. miR-203 can be used as a predictor for progression and prognosis of BC patients treated with cisplatin based chemotherapy. Moreover, overexpression of miR-203 can enhance cisplatin sensitization by promoting apoptosis via directly targeting Bcl-w and Survivin.

Disease Class: Ovarian cancer [ICD-11: 2C73.0] [6]

• Sensitive Disease: Ovarian cancer [ICD-11: 2C73.0]
• Sensitive 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: SkOV3 cells; Ovary; Homo sapiens (Human); CVCL_0532
• In Vitro Model: OVCAR3 cells; Ovary; Homo sapiens (Human); CVCL_0465
• Experiment for Molecule Alteration: Dual luciferase reporter assay; Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: microRNA 146a 5p enhances cisplatin induced apoptosis in ovarian cancer cells by targeting multiple anti apoptotic genes, including XIAP, BCL2L2 and BIRC5 via their 3'UTRs.

Disease Class: Cervical cancer [ICD-11: 2C77.0] [7]

• Sensitive Disease: Cervical cancer [ICD-11: 2C77.0]
• Sensitive Drug: Cisplatin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: Hela cells; Cervix uteri; Homo sapiens (Human); CVCL_0030
• In Vitro Model: C33A cells; Uterus; Homo sapiens (Human); CVCL_1094
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-214 significantly reduced cell survival and rendered cell sensitivity to cisplatin through inhibiting the anti-apoptotic protein Bcl2l2.

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [5]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: RWPE-1 cells; Prostate; Homo sapiens (Human); CVCL_3791
• In Vitro Model: 22RV1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• In Vitro Model: VCaP cells; Prostate; Homo sapiens (Human); CVCL_2235
• In Vitro Model: WPE1-NA22 cells; Prostate; Homo sapiens (Human); CVCL_3810
• In Vitro Model: WPE1-NB11 cells; Prostate; Homo sapiens (Human); CVCL_3811
• In Vitro Model: WPE1-NB14 cells; Prostate; Homo sapiens (Human); CVCL_3812
• In Vitro Model: WPE1-NB26 cells; Prostate; Homo sapiens (Human); CVCL_3813
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [5]

• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: DU-145 cells; Prostate; Homo sapiens (Human); CVCL_0105
• In Vitro Model: LNCaP cells; Prostate; Homo sapiens (Human); CVCL_0395
• In Vitro Model: PC3 cells; Prostate; Homo sapiens (Human); CVCL_0035
• In Vitro Model: RWPE-1 cells; Prostate; Homo sapiens (Human); CVCL_3791
• In Vitro Model: 22RV1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• In Vitro Model: VCaP cells; Prostate; Homo sapiens (Human); CVCL_2235
• In Vitro Model: WPE1-NA22 cells; Prostate; Homo sapiens (Human); CVCL_3810
• In Vitro Model: WPE1-NB11 cells; Prostate; Homo sapiens (Human); CVCL_3811
• In Vitro Model: WPE1-NB14 cells; Prostate; Homo sapiens (Human); CVCL_3812
• In Vitro Model: WPE1-NB26 cells; Prostate; Homo sapiens (Human); CVCL_3813
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Flow cytometry assay
• Mechanism Description: miR-205 and miR-31 regulate apoptosis in prostate cancer cells by targeting antiapoptotic proteins Bcl-w and E2F6.

Venetoclax

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Diffuse large B-cell lymphoma [ICD-11: 2A81.0] [8]

• Resistant Disease: Diffuse large B-cell lymphoma [ICD-11: 2A81.0]
• Resistant Drug: Venetoclax
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Apoptosis signaling pathway; Inhibition; hsa04210
• In Vitro Model: SU-DHL-2 cells; N.A.; Homo sapiens (Human); CVCL_9950
• In Vitro Model: SUDHL4 cells; Blood; Homo sapiens (Human); CVCL_0539
• In Vitro Model: SUDHL5 cells; Blood; Homo sapiens (Human); CVCL_1735
• In Vitro Model: SUDHL6 cells; Blood; Homo sapiens (Human); CVCL_2206
• In Vitro Model: SUDHL8 cells; Blood; Homo sapiens (Human); CVCL_2207
• In Vitro Model: SUDHL10 cells; Blood; Homo sapiens (Human); CVCL_1889
• In Vitro Model: SUDHL16 cells; Blood; Homo sapiens (Human); CVCL_1890
• In Vitro Model: Toledo cells; Peripheral blood; Homo sapiens (Human); CVCL_3611
• Experiment for Molecule Alteration: Western blot assay; RNA Sequencing assay; Flow cytometry
• Experiment for Drug Resistance: Cell survival and synergy assay; Caspase-3/7 apoptosis assay; Live/Dead assay
• Mechanism Description: Our findings demonstrate that multiple, complex mechanisms of venetoclax resistance can emerge in DLBCL. However, our elucidation of the increased vulnerability of venetoclax-resistant DLBCL to ETC complex I and IDH2 inhibition revealed potential new treatment approaches to overcome venetoclax resistance. Although there is still interest in adding venetoclax to decrease the threshold of apoptosis in the therapeutic armamentarium for DLBCL as a combination therapy, targeting other BCL2 family members, such as BCLW and BFL1, for which there are currently no specific targeted agents, could also be an option.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Colon cancer [ICD-11: 2B90]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Colon
• The Specified Disease: Colon cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.40E-42; Fold-change: -4.44E-01; Z-score: -1.70E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 2.15E-06; Fold-change: -1.62E-01; Z-score: -4.62E-01

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 9.79E-03; Fold-change: -1.59E-01; Z-score: -5.39E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.32E-20; Fold-change: 2.16E-01; Z-score: 1.10E+00
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 5.77E-03; Fold-change: -2.15E-01; Z-score: -2.67E+00

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: 1.83E-48; Fold-change: -6.94E-01; Z-score: -1.67E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 1.19E-28; Fold-change: -7.04E-01; Z-score: -1.56E+00

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: 7.30E-01; Fold-change: 1.54E-02; Z-score: 5.13E-02
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 8.89E-01; Fold-change: 8.34E-02; Z-score: 1.61E-01

Cervical cancer [ICD-11: 2C77]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Cervix uteri
• The Specified Disease: Cervical cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.19E-04; Fold-change: -3.01E-01; Z-score: -1.32E+00

Prostate cancer [ICD-11: 2C82]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Prostate
• The Specified Disease: Prostate cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.57E-02; Fold-change: -4.88E-01; Z-score: -8.30E-01

Bladder cancer [ICD-11: 2C94]

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: 2.27E-03; Fold-change: -8.72E-01; Z-score: -1.65E+00

References

• Ref 1: miRNA-195 sensitizes human hepatocellular carcinoma cells to 5-FU by targeting BCL-w. Oncol Rep. 2012 Jan;27(1):250-7. doi: 10.3892/or.2011.1472. Epub 2011 Sep 22.
• Ref 2: MicroRNA-195 chemosensitizes colon cancer cells to the chemotherapeutic drug doxorubicin by targeting the first binding site of BCL2L2 mRNA. J Cell Physiol. 2015 Mar;230(3):535-45. doi: 10.1002/jcp.24366.
• Ref 3: MiRNA-107 enhances chemosensitivity to paclitaxel by targeting antiapoptotic factor Bcl-w in non small cell lung cancer. Am J Cancer Res. 2017 Sep 1;7(9):1863-1873. eCollection 2017.
• Ref 4: MicroRNA-203 Is a Prognostic Indicator in Bladder Cancer and Enhances Chemosensitivity to Cisplatin via Apoptosis by Targeting Bcl-w and Survivin. PLoS One. 2015 Nov 23;10(11):e0143441. doi: 10.1371/journal.pone.0143441. eCollection 2015.
• Ref 5: Downregulation of miR-205 and miR-31 confers resistance to chemotherapy-induced apoptosis in prostate cancer cells. Cell Death Dis. 2010 Dec 9;1(12):e105. doi: 10.1038/cddis.2010.85.
• Ref 6: MicroRNA 146a 5p enhances cisplatin induced apoptosis in ovarian cancer cells by targeting multiple anti apoptotic genes. Int J Oncol. 2017 Jul;51(1):327-335. doi: 10.3892/ijo.2017.4023. Epub 2017 May 29.
• Ref 7: MiR-214 reduces cell survival and enhances cisplatin-induced cytotoxicity via down-regulation of Bcl2l2 in cervical cancer cells. FEBS Lett. 2013 Mar 1;587(5):488-95. doi: 10.1016/j.febslet.2013.01.016. Epub 2013 Jan 18.
• Ref 8: Identifying Targetable Vulnerabilities to Circumvent or Overcome Venetoclax Resistance in Diffuse Large B-Cell Lymphoma. Cancers (Basel). 2024 Jun 3;16(11):2130.