Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0VVG4V)

DOT Name Inhibitor of growth protein 4 (ING4)
Synonyms p29ING4
Gene Name ING4
Related Disease
Lung adenocarcinoma ( )
Adenocarcinoma ( )
Advanced cancer ( )
Astrocytoma ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Brain neoplasm ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Colon cancer ( )
Colon carcinoma ( )
Colorectal carcinoma ( )
Colorectal neoplasm ( )
Diabetic retinopathy ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Glioma ( )
Head-neck squamous cell carcinoma ( )
Hepatocellular carcinoma ( )
Lung cancer ( )
Lung carcinoma ( )
Osteosarcoma ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Prostate neoplasm ( )
Pulmonary fibrosis ( )
Squamous cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Cervical cancer ( )
Cervical carcinoma ( )
Clear cell renal carcinoma ( )
Gastric adenocarcinoma ( )
Head and neck cancer ( )
Head and neck carcinoma ( )
Metastatic malignant neoplasm ( )
Stomach cancer ( )
Adult glioblastoma ( )
Glioblastoma multiforme ( )
Melanoma ( )
Nasopharyngeal carcinoma ( )
Non-small-cell lung cancer ( )
Pancreatic cancer ( )
Plasma cell myeloma ( )
Prostate cancer ( )
Prostate carcinoma ( )
Renal cell carcinoma ( )
Small lymphocytic lymphoma ( )
UniProt ID
ING4_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2K1J; 2M1R; 2PNX; 2VNF; 4AFL
Pfam ID
PF12998
Sequence
MAAGMYLEHYLDSIENLPFELQRNFQLMRDLDQRTEDLKAEIDKLATEYMSSARSLSSEE
KLALLKQIQEAYGKCKEFGDDKVQLAMQTYEMVDKHIRRLDTDLARFEADLKEKQIESSD
YDSSSSKGKKKGRTQKEKKAARARSKGKNSDEEAPKTAQKKLKLVRTSPEYGMPSVTFGS
VHPSDVLDMPVDPNEPTYCLCHQVSYGEMIGCDNPDCSIEWFHFACVGLTTKPRGKWFCP
RCSQERKKK
Function
Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4. Through chromatin acetylation it may function in DNA replication. May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation. Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA. May also specifically suppress loss of contact inhibition elicited by activated oncogenes such as MYC. Represses hypoxia inducible factor's (HIF) activity by interacting with HIF prolyl hydroxylase 2 (EGLN1). Can enhance apoptosis induced by serum starvation in mammary epithelial cell line HC11.
Reactome Pathway
HATs acetylate histones (R-HSA-3214847 )

Molecular Interaction Atlas (MIA) of This DOT

49 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Lung adenocarcinoma DISD51WR Definitive Biomarker [1]
Adenocarcinoma DIS3IHTY Strong Altered Expression [2]
Advanced cancer DISAT1Z9 Strong Altered Expression [3]
Astrocytoma DISL3V18 Strong Biomarker [4]
Bladder cancer DISUHNM0 Strong Altered Expression [5]
Bone osteosarcoma DIST1004 Strong Biomarker [6]
Brain neoplasm DISY3EKS Strong Biomarker [7]
Breast cancer DIS7DPX1 Strong Biomarker [8]
Breast carcinoma DIS2UE88 Strong Biomarker [9]
Breast neoplasm DISNGJLM Strong Altered Expression [8]
Colon cancer DISVC52G Strong Biomarker [10]
Colon carcinoma DISJYKUO Strong Biomarker [10]
Colorectal carcinoma DIS5PYL0 Strong Altered Expression [11]
Colorectal neoplasm DISR1UCN Strong Therapeutic [12]
Diabetic retinopathy DISHGUJM Strong Biomarker [13]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [14]
Gastric cancer DISXGOUK Strong Biomarker [15]
Glioma DIS5RPEH Strong Biomarker [16]
Head-neck squamous cell carcinoma DISF7P24 Strong Biomarker [17]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [3]
Lung cancer DISCM4YA Strong Biomarker [18]
Lung carcinoma DISTR26C Strong Biomarker [18]
Osteosarcoma DISLQ7E2 Strong Biomarker [6]
Ovarian cancer DISZJHAP Strong Biomarker [14]
Ovarian neoplasm DISEAFTY Strong Biomarker [14]
Prostate neoplasm DISHDKGQ Strong Biomarker [19]
Pulmonary fibrosis DISQKVLA Strong Altered Expression [20]
Squamous cell carcinoma DISQVIFL Strong Altered Expression [21]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [5]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [5]
Cervical cancer DISFSHPF moderate Altered Expression [22]
Cervical carcinoma DIST4S00 moderate Altered Expression [22]
Clear cell renal carcinoma DISBXRFJ moderate Altered Expression [23]
Gastric adenocarcinoma DISWWLTC moderate Biomarker [24]
Head and neck cancer DISBPSQZ moderate Biomarker [25]
Head and neck carcinoma DISOU1DS moderate Biomarker [25]
Metastatic malignant neoplasm DIS86UK6 moderate Biomarker [22]
Stomach cancer DISKIJSX moderate Biomarker [15]
Adult glioblastoma DISVP4LU Disputed Altered Expression [26]
Glioblastoma multiforme DISK8246 Disputed Altered Expression [26]
Melanoma DIS1RRCY Disputed Biomarker [27]
Nasopharyngeal carcinoma DISAOTQ0 Limited Biomarker [28]
Non-small-cell lung cancer DIS5Y6R9 Limited Biomarker [29]
Pancreatic cancer DISJC981 Limited Biomarker [30]
Plasma cell myeloma DIS0DFZ0 Limited Biomarker [31]
Prostate cancer DISF190Y Limited Biomarker [32]
Prostate carcinoma DISMJPLE Limited Biomarker [32]
Renal cell carcinoma DISQZ2X8 Limited Altered Expression [23]
Small lymphocytic lymphoma DIS30POX Limited Biomarker [33]
------------------------------------------------------------------------------------
⏷ Show the Full List of 49 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Inhibitor of growth protein 4 (ING4). [34]
Ciclosporin DMAZJFX Approved Ciclosporin decreases the expression of Inhibitor of growth protein 4 (ING4). [35]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Inhibitor of growth protein 4 (ING4). [36]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Inhibitor of growth protein 4 (ING4). [37]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Inhibitor of growth protein 4 (ING4). [38]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Inhibitor of growth protein 4 (ING4). [39]
Ethanol DMDRQZU Approved Ethanol decreases the expression of Inhibitor of growth protein 4 (ING4). [40]
GSK2110183 DMZHB37 Phase 2 GSK2110183 increases the expression of Inhibitor of growth protein 4 (ING4). [41]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the expression of Inhibitor of growth protein 4 (ING4). [42]
(+)-JQ1 DM1CZSJ Phase 1 (+)-JQ1 increases the expression of Inhibitor of growth protein 4 (ING4). [43]
Leflunomide DMR8ONJ Phase 1 Trial Leflunomide decreases the expression of Inhibitor of growth protein 4 (ING4). [44]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Inhibitor of growth protein 4 (ING4). [45]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Inhibitor of growth protein 4 (ING4). [46]
Milchsaure DM462BT Investigative Milchsaure decreases the expression of Inhibitor of growth protein 4 (ING4). [47]
------------------------------------------------------------------------------------
⏷ Show the Full List of 14 Drug(s)

References

1 Identification of ING4 (inhibitor of growth 4) as a modulator of docetaxel sensitivity in human lung adenocarcinoma.Mol Med. 2012 Jul 18;18(1):874-86. doi: 10.2119/molmed.2011.00230.
2 ING4 induces cell growth inhibition in human lung adenocarcinoma A549 cells by means of Wnt-1/beta-catenin signaling pathway. Anat Rec (Hoboken). 2008 May;291(5):593-600.
3 ING4 suppresses hepatocellular carcinoma via a NF-B/miR-155/FOXO3a signaling axis.Int J Biol Sci. 2019 Jan 1;15(2):369-385. doi: 10.7150/ijbs.28422. eCollection 2019.
4 Loss of inhibitor of growth (ING-4) is implicated in the pathogenesis and progression of human astrocytomas.Brain Pathol. 2010 Mar;20(2):490-7. doi: 10.1111/j.1750-3639.2009.00325.x. Epub 2009 Aug 6.
5 Reduced ING4 Expression Is Associated with the Malignancy of Human Bladder.Urol Int. 2015;94(4):464-71. doi: 10.1159/000364832. Epub 2015 Mar 14.
6 Adenovirus-mediated ING4 Gene Transfer in Osteosarcoma Suppresses Tumor Growth via Induction of Apoptosis and Inhibition of Tumor Angiogenesis.Technol Cancer Res Treat. 2015 Aug;14(4):369-78. doi: 10.1177/1533034614500424. Epub 2014 Oct 16.
7 The candidate tumour suppressor protein ING4 regulates brain tumour growth and angiogenesis.Nature. 2004 Mar 18;428(6980):328-32. doi: 10.1038/nature02329.
8 Differential cellular localization of CELSR2 and ING4 and correlations with hormone receptor status in breast cancer.Histol Histopathol. 2018 Aug;33(8):835-842. doi: 10.14670/HH-11-979. Epub 2018 Feb 28.
9 Oncogenic microRNA-765 promotes the growth and metastasis of breast carcinoma by directly targeting ING4.J Cell Biochem. 2020 Aug;121(8-9):3887-3900. doi: 10.1002/jcb.29545. Epub 2019 Nov 13.
10 ING4 is negatively correlated with microvessel density in colon cancer.Tumour Biol. 2012 Dec;33(6):2357-64. doi: 10.1007/s13277-012-0498-9. Epub 2012 Sep 28.
11 Long non-coding RNA FENDRR restrains the aggressiveness of CRC via regulating miR-18a-5p/ING4 axis.J Cell Biochem. 2020 Aug;121(8-9):3973-3985. doi: 10.1002/jcb.29555. Epub 2019 Nov 13.
12 ING4 suppresses tumor angiogenesis and functions as a prognostic marker in human colorectal cancer.Oncotarget. 2016 Nov 29;7(48):79017-79031. doi: 10.18632/oncotarget.12984.
13 Inhibitor of growth 4 affects hypoxia-induced migration and angiogenesis regulation in retinal pigment epithelial cells.J Cell Physiol. 2019 Sep;234(9):15243-15256. doi: 10.1002/jcp.28170. Epub 2019 Jan 22.
14 Combinatorial strategies based on CRAd-IL24 and CRAd-ING4 virotherapy with anti-angiogenesis treatment for ovarian cancer.J Ovarian Res. 2016 Jun 27;9(1):38. doi: 10.1186/s13048-016-0248-5.
15 N-methyl-N-nitro-N-nitrosoguanidine-mediated ING4 downregulation contributed to the angiogenesis of transformed human gastric epithelial cells.Life Sci. 2018 Apr 15;199:179-187. doi: 10.1016/j.lfs.2018.02.034. Epub 2018 Feb 26.
16 Synergistic antitumor effect of ING4/PTEN double tumor suppressors mediated by adenovirus modified with arginine-glycine-aspartate on glioma.J Neurosurg Sci. 2020 Apr;64(2):173-180. doi: 10.23736/S0390-5616.17.03978-9. Epub 2017 Apr 12.
17 Downregulation and translocation of nuclear ING4 is correlated with tumorigenesis and progression of head and neck squamous cell carcinoma.Oral Oncol. 2011 Mar;47(3):217-23. doi: 10.1016/j.oraloncology.2011.01.004.
18 MicroRNA?14 upregulates HIF? and VEGF by targeting ING4 in lung cancer cells.Mol Med Rep. 2019 Jun;19(6):4935-4945. doi: 10.3892/mmr.2019.10170. Epub 2019 Apr 16.
19 Miz1, a Novel Target of ING4, Can Drive Prostate Luminal Epithelial Cell Differentiation.Prostate. 2017 Jan;77(1):49-59. doi: 10.1002/pros.23249. Epub 2016 Aug 16.
20 Expression of HIF-1A/VEGF/ING-4 Axis in Pulmonary Sarcoidosis.Adv Exp Med Biol. 2015;866:61-9. doi: 10.1007/5584_2015_144.
21 Frequent deletion and down-regulation of ING4, a candidate tumor suppressor gene at 12p13, in head and neck squamous cell carcinomas.Gene. 2005 Aug 15;356:109-17. doi: 10.1016/j.gene.2005.02.014.
22 The expression of inhibitor of growth 4 is reduced in cervical cancer tissues.Eur Rev Med Pharmacol Sci. 2016 Jul;20(15):3178-85.
23 Inhibitor of growth 4 inhibits cell proliferation, migration, and induces apoptosis of renal cell carcinoma cells.J Cell Biochem. 2019 Apr;120(4):6709-6717. doi: 10.1002/jcb.27967. Epub 2018 Nov 2.
24 Down-regulation of ING4 is associated with initiation and progression of lung cancer.Histopathology. 2010 Aug;57(2):271-81. doi: 10.1111/j.1365-2559.2010.03623.x.
25 Tumor-specific mutation and downregulation of ING5 detected in oral squamous cell carcinoma.Int J Cancer. 2010 Nov 1;127(9):2088-94. doi: 10.1002/ijc.25224.
26 Inhibitor of growth 4 suppresses cell spreading and cell migration by interacting with a novel binding partner, liprin alpha1.Cancer Res. 2007 Mar 15;67(6):2552-8. doi: 10.1158/0008-5472.CAN-06-3870.
27 Role of inhibitor of growth 4 in the suppression of human melanoma cells through the Fas/FasL-mediated apoptosis pathway.Int J Mol Med. 2018 Feb;41(2):1055-1061. doi: 10.3892/ijmm.2017.3274. Epub 2017 Nov 20.
28 Adenovirus-mediated co-expression of ING4 and PTEN cooperatively enhances their antitumor activity in human hepatocellular carcinoma cells.Acta Biochim Biophys Sin (Shanghai). 2016 Aug;48(8):704-13. doi: 10.1093/abbs/gmw062. Epub 2016 Jul 14.
29 miR-650 promotes non-small cell lung cancer cell proliferation and invasion by targeting ING4 through Wnt-1/-catenin pathway.Oncol Lett. 2019 Nov;18(5):4621-4628. doi: 10.3892/ol.2019.10805. Epub 2019 Sep 4.
30 Synergistic antitumor effect of adenovirus-mediated hING4 gene therapy and (125)I radiation therapy on pancreatic cancer.Cancer Lett. 2012 Mar 28;316(2):211-8. doi: 10.1016/j.canlet.2011.11.003. Epub 2011 Nov 7.
31 The inhibitor of growth 1 (ING1) proteins suppress angiogenesis and differentially regulate angiopoietin expression in glioblastoma cells.Oncol Res. 2009;18(2-3):95-105. doi: 10.3727/096504009789954645.
32 Identification of the inhibitor of growth protein 4 (ING4) as a potential target in prostate cancer therapy.Mol Cell Biochem. 2020 Jan;464(1-2):153-167. doi: 10.1007/s11010-019-03657-x. Epub 2019 Nov 27.
33 Cytokinesis arrest and multiple centrosomes in B cell chronic lymphocytic leukaemia.J Cell Mol Med. 2018 May;22(5):2846-2855. doi: 10.1111/jcmm.13579. Epub 2018 Mar 7.
34 Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
35 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
36 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
37 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
38 Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
39 Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells. Front Physiol. 2016 Nov 24;7:559. doi: 10.3389/fphys.2016.00559. eCollection 2016.
40 Gene expression signatures after ethanol exposure in differentiating embryoid bodies. Toxicol In Vitro. 2018 Feb;46:66-76.
41 Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
42 Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
43 BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J Leukoc Biol. 2012 Dec;92(6):1147-54. doi: 10.1189/jlb.0312165. Epub 2012 Jul 16.
44 Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
45 Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
46 A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
47 Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.