Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUC5CDB)

DOT Name Krueppel-like factor 8 (KLF8)
Synonyms Basic krueppel-like factor 3; Zinc finger protein 741
Gene Name KLF8
Related Disease
Adult glioblastoma ( )
Advanced cancer ( )
Alzheimer disease ( )
Bladder cancer ( )
Bone osteosarcoma ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Clear cell renal carcinoma ( )
Colorectal carcinoma ( )
Glioma ( )
Hepatocellular carcinoma ( )
Kidney cancer ( )
Lung cancer ( )
Lung carcinoma ( )
Malignant glioma ( )
Non-small-cell lung cancer ( )
Osteosarcoma ( )
Ovarian neoplasm ( )
Renal carcinoma ( )
Renal cell carcinoma ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Carcinoma ( )
Lung adenocarcinoma ( )
Pancreatic cancer ( )
Alopecia ( )
Epithelial ovarian cancer ( )
Gastric cancer ( )
Intellectual disability ( )
Metastatic malignant neoplasm ( )
Neoplasm ( )
Ovarian cancer ( )
Prostate cancer ( )
Prostate carcinoma ( )
Stomach cancer ( )
UniProt ID
KLF8_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Pfam ID
PF00096
Sequence
MVDMDKLINNLEVQLNSEGGSMQVFKQVTASVRNRDPPEIEYRSNMTSPTLLDANPMENP
ALFNDIKIEPPEELLASDFSLPQVEPVDLSFHKPKAPLQPASMLQAPIRPPKPQSSPQTL
VVSTSTSDMSTSANIPTVLTPGSVLTSSQSTGSQQILHVIHTIPSVSLPNKMGGLKTIPV
VVQSLPMVYTTLPADGGPAAITVPLIGGDGKNAGSVKVDPTSMSPLEIPSDSEESTIESG
SSALQSLQGLQQEPAAMAQMQGEESLDLKRRRIHQCDFAGCSKVYTKSSHLKAHRRIHTG
EKPYKCTWDGCSWKFARSDELTRHFRKHTGIKPFRCTDCNRSFSRSDHLSLHRRRHDTM
Function
Transcriptional repressor and activator. Binds to CACCC-boxes promoter elements. Also binds the GT-box of cyclin D1 promoter and mediates cell cycle progression at G(1) phase as a downstream target of focal adhesion kinase (FAK).
Tissue Specificity Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

36 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Adult glioblastoma DISVP4LU Strong Biomarker [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Altered Expression [3]
Bladder cancer DISUHNM0 Strong Biomarker [4]
Bone osteosarcoma DIST1004 Strong Biomarker [5]
Breast cancer DIS7DPX1 Strong Altered Expression [6]
Breast carcinoma DIS2UE88 Strong Altered Expression [6]
Breast neoplasm DISNGJLM Strong Altered Expression [7]
Clear cell renal carcinoma DISBXRFJ Strong Altered Expression [8]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [9]
Glioma DIS5RPEH Strong Biomarker [10]
Hepatocellular carcinoma DIS0J828 Strong Biomarker [11]
Kidney cancer DISBIPKM Strong Altered Expression [12]
Lung cancer DISCM4YA Strong Biomarker [13]
Lung carcinoma DISTR26C Strong Biomarker [13]
Malignant glioma DISFXKOV Strong Biomarker [14]
Non-small-cell lung cancer DIS5Y6R9 Strong Biomarker [15]
Osteosarcoma DISLQ7E2 Strong Biomarker [5]
Ovarian neoplasm DISEAFTY Strong Altered Expression [16]
Renal carcinoma DISER9XT Strong Altered Expression [12]
Renal cell carcinoma DISQZ2X8 Strong Biomarker [14]
Urinary bladder cancer DISDV4T7 Strong Biomarker [4]
Urinary bladder neoplasm DIS7HACE Strong Biomarker [4]
Carcinoma DISH9F1N moderate Altered Expression [17]
Lung adenocarcinoma DISD51WR moderate Biomarker [18]
Pancreatic cancer DISJC981 moderate Biomarker [19]
Alopecia DIS37HU4 Limited Genetic Variation [20]
Epithelial ovarian cancer DIS56MH2 Limited Altered Expression [21]
Gastric cancer DISXGOUK Limited Biomarker [22]
Intellectual disability DISMBNXP Limited Biomarker [23]
Metastatic malignant neoplasm DIS86UK6 Limited Altered Expression [19]
Neoplasm DISZKGEW Limited Altered Expression [17]
Ovarian cancer DISZJHAP Limited Altered Expression [21]
Prostate cancer DISF190Y Limited Biomarker [24]
Prostate carcinoma DISMJPLE Limited Biomarker [24]
Stomach cancer DISKIJSX Limited Biomarker [22]
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⏷ Show the Full List of 36 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Krueppel-like factor 8 (KLF8). [25]
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Krueppel-like factor 8 (KLF8). [26]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Krueppel-like factor 8 (KLF8). [27]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Krueppel-like factor 8 (KLF8). [28]
Calcitriol DM8ZVJ7 Approved Calcitriol increases the expression of Krueppel-like factor 8 (KLF8). [29]
Gemcitabine DMSE3I7 Approved Gemcitabine increases the expression of Krueppel-like factor 8 (KLF8). [30]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Krueppel-like factor 8 (KLF8). [32]
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⏷ Show the Full List of 7 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Krueppel-like factor 8 (KLF8). [31]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Krueppel-like factor 8 (KLF8). [33]
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References

1 Small interfering RNA targeting Krppel-like factor 8 inhibits U251 glioblastoma cell growth by inducing apoptosis.Mol Med Rep. 2012 Feb;5(2):347-50. doi: 10.3892/mmr.2011.669. Epub 2011 Nov 8.
2 Regulation of Krppel-like factor 8 by the NEDD4 E3 ubiquitin ligase.Am J Transl Res. 2019 Mar 15;11(3):1521-1530. eCollection 2019.
3 Krppel-like factor 8 ameliorates Alzheimer's disease by activating -catenin.J Mol Neurosci. 2014 Feb;52(2):231-41. doi: 10.1007/s12031-013-0131-4. Epub 2013 Oct 11.
4 The lncRNA ELF3-AS1 promotes bladder cancer progression by interaction with Krppel-like factor 8.Biochem Biophys Res Commun. 2019 Jan 15;508(3):762-768. doi: 10.1016/j.bbrc.2018.11.183. Epub 2018 Dec 7.
5 Upregulated miRNA-1236-3p in osteosarcoma inhibits cell proliferation and induces apoptosis via targeting KLF8.Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6053-6061. doi: 10.26355/eurrev_201907_18418.
6 KLF8 and FAK cooperatively enrich the active MMP14 on the cell surface required for the metastatic progression of breast cancer.Oncogene. 2014 May 29;33(22):2909-17. doi: 10.1038/onc.2013.247. Epub 2013 Jul 1.
7 Krppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion.Cancer Res. 2007 Aug 1;67(15):7184-93. doi: 10.1158/0008-5472.CAN-06-4729.
8 Krppel-like factor 8 contributes to hypoxia-induced MDR in gastric cancer cells.Cancer Sci. 2014 Sep;105(9):1109-15. doi: 10.1111/cas.12483. Epub 2014 Sep 8.
9 KLF8 promotes tumorigenesis, invasion and metastasis of colorectal cancer cells by transcriptional activation of FHL2.Oncotarget. 2015 Sep 22;6(28):25402-17. doi: 10.18632/oncotarget.4517.
10 KLF8 Promotes Temozolomide Resistance in Glioma Cells via -Catenin Activation.Cell Physiol Biochem. 2016;38(4):1596-604. doi: 10.1159/000443100. Epub 2016 Apr 18.
11 Krppel-like factor 8 regulates VEGFA expression and angiogenesis in hepatocellular carcinoma.Sci Rep. 2018 Nov 27;8(1):17415. doi: 10.1038/s41598-018-35786-6.
12 Expression of Kruppel-like factor 8 and Ki67 in lung adenocarcinoma and prognosis.Exp Ther Med. 2017 Aug;14(2):1351-1356. doi: 10.3892/etm.2017.4632. Epub 2017 Jun 20.
13 KLF8 overexpression promotes the growth of human lung cancer cells by promoting the expression of JMJD2A.Cancer Cell Int. 2019 Oct 7;19:258. doi: 10.1186/s12935-019-0970-3. eCollection 2019.
14 Krppel-like factor 8 (KLF8) is expressed in gliomas of different WHO grades and is essential for tumor cell proliferation.PLoS One. 2012;7(1):e30429. doi: 10.1371/journal.pone.0030429. Epub 2012 Jan 19.
15 Krppel-Like Factor 8 Overexpression Correlates with Poor Prognosis in Non-Small Cell Lung Cancer.Pathol Oncol Res. 2019 Jan;25(1):115-121. doi: 10.1007/s12253-017-0321-4. Epub 2017 Oct 6.
16 Activation of KLF8 transcription by focal adhesion kinase in human ovarian epithelial and cancer cells.J Biol Chem. 2008 May 16;283(20):13934-42. doi: 10.1074/jbc.M709300200. Epub 2008 Mar 19.
17 The level of Krppel-like factor 8 expression predicts prognosis and metastasis in various carcinomas.Medicine (Baltimore). 2019 May;98(18):e15519. doi: 10.1097/MD.0000000000015519.
18 miR-1236-3p suppresses the migration and invasion by targeting KLF8 in lung adenocarcinoma A549cells.Biochem Biophys Res Commun. 2017 Oct 21;492(3):461-467. doi: 10.1016/j.bbrc.2017.08.074. Epub 2017 Aug 24.
19 Krppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2.Oncol Lett. 2017 Oct;14(4):4883-4889. doi: 10.3892/ol.2017.6734. Epub 2017 Aug 9.
20 Genetic prediction of male pattern baldness.PLoS Genet. 2017 Feb 14;13(2):e1006594. doi: 10.1371/journal.pgen.1006594. eCollection 2017 Feb.
21 Transformation of human ovarian surface epithelial cells by Krppel-like factor 8.Oncogene. 2014 Jan 2;33(1):10-8. doi: 10.1038/onc.2012.545. Epub 2012 Dec 10.
22 KLF8 is associated with poor prognosis and regulates glycolysis by targeting GLUT4 in gastric cancer.J Cell Mol Med. 2019 Aug;23(8):5087-5097. doi: 10.1111/jcmm.14378. Epub 2019 May 24.
23 Abnormal expression of the KLF8 (ZNF741) gene in a female patient with an X;autosome translocation t(X;21)(p11.2;q22.3) and non-syndromic mental retardation.J Med Genet. 2002 Feb;39(2):113-7. doi: 10.1136/jmg.39.2.113.
24 Krppel-like factor 8 is a novel androgen receptor co-activator in human prostate cancer.Acta Pharmacol Sin. 2013 Feb;34(2):282-8. doi: 10.1038/aps.2012.130. Epub 2012 Oct 1.
25 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
26 Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
27 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.
28 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
29 Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
30 Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
31 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
32 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
33 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.