Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTZ7FIU8)

• DOT Name: Sialomucin core protein 24 (CD164)
• Synonyms: MUC-24; Endolyn; Multi-glycosylated core protein 24; MGC-24; MGC-24v; CD antigen CD164
• Gene Name: CD164
• Related Disease:
  Aplastic anemia
  Adenocarcinoma
  Adult glioblastoma
  Advanced cancer
  Bladder cancer
  Brain neoplasm
  Deafness
  Glioblastoma multiforme
  Glioma
  Neoplasm
  Oral cavity squamous cell carcinoma
  Primary cutaneous T-cell lymphoma
  Primary myelofibrosis
  Prostate cancer
  Prostate carcinoma
  Prostate neoplasm
  Sezary syndrome
  Urinary bladder cancer
  Urinary bladder neoplasm
  Autosomal dominant nonsyndromic hearing loss
  Autosomal dominant nonsyndromic hearing loss 66
  Carcinoma
  Colorectal carcinoma
  Epithelial ovarian cancer
  Lung cancer
  Lung carcinoma
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: MUC24_HUMAN
• Pfam ID: PF05283
• Sequence:
  MSRLSRSLLWAATCLGVLCVLSADKNTTQHPNVTTLAPISNVTSAPVTSLPLVTTPAPET
  CEGRNSCVSCFNVSVVNTTCFWIECKDESYCSHNSTVSDCQVGNTTDFCSVSTATPVPTA
  NSTAKPTVQPSPSTTSKTVTTSGTTNNTVTPTSQPVRKSTFDAASFIGGIVLVLGVQAVI
  FFLYKFCKSKERNYHTL
• Function: Sialomucin that may play a key role in hematopoiesis by facilitating the adhesion of CD34(+) cells to the stroma and by negatively regulating CD34(+)CD38(lo/-) cell proliferation. Modulates the migration of umbilical cord blood CD133+ cells and this is mediated through the CXCL12/CXCR4 axis. May play an important role in prostate cancer metastasis and the infiltration of bone marrow by cancer cells. Promotes myogenesis by enhancing CXCR4-dependent cell motility. Positively regulates myoblast migration and promotes myoblast fusion into myotubes.
• Tissue Specificity: Isoform 1 and isoform 3 are expressed in hematopoietic and non-hematopoietic tissues. Isoform 1 is expressed by prostate cancer tumors and prostate cancer cell lines. The expression is greater in bone metastases than in primary tumors. Expression in osseous metastasis is greater than that in soft tissue metastasis. Isoform 2 is expressed in the small intestine, colon, lung, thyroid and in colorectal and pancreatic adenocarcinoma. Isoform 4 is expressed by both hematopoietic progenitor cells and bone marrow stromal cells.
• KEGG Pathway: Lysosome (hsa04142)

Molecular Interaction Atlas (MIA) of This DOT

28 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Aplastic anemia	DISJRSC0	Definitive	Altered Expression	[1]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[2]
Adult glioblastoma	DISVP4LU	Strong	Altered Expression	[3]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[4]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[5]
Brain neoplasm	DISY3EKS	Strong	Biomarker	[3]
Deafness	DISKCLH4	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Altered Expression	[3]
Glioma	DIS5RPEH	Strong	Altered Expression	[3]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Oral cavity squamous cell carcinoma	DISQVJVA	Strong	Altered Expression	[7]
Primary cutaneous T-cell lymphoma	DIS35WVW	Strong	Altered Expression	[4]
Primary myelofibrosis	DIS6L0CN	Strong	Altered Expression	[8]
Prostate cancer	DISF190Y	Strong	Biomarker	[9]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[9]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[10]
Sezary syndrome	DISFMTC7	Strong	Biomarker	[4]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[5]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[5]
Autosomal dominant nonsyndromic hearing loss	DISYC1G0	Supportive	Autosomal dominant	[6]
Autosomal dominant nonsyndromic hearing loss 66	DIS9FY16	Limited	Autosomal dominant	[6]
Carcinoma	DISH9F1N	Limited	Altered Expression	[11]
Colorectal carcinoma	DIS5PYL0	Limited	Altered Expression	[11]
Epithelial ovarian cancer	DIS56MH2	Limited	Biomarker	[12]
Lung cancer	DISCM4YA	Limited	Altered Expression	[13]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[13]
Ovarian cancer	DISZJHAP	Limited	Biomarker	[12]
Ovarian neoplasm	DISEAFTY	Limited	Biomarker	[12]

15 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Sialomucin core protein 24 (CD164).	[14]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Sialomucin core protein 24 (CD164).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Sialomucin core protein 24 (CD164).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Sialomucin core protein 24 (CD164).	[17]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Sialomucin core protein 24 (CD164).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Sialomucin core protein 24 (CD164).	[19]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Sialomucin core protein 24 (CD164).	[20]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Sialomucin core protein 24 (CD164).	[21]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Sialomucin core protein 24 (CD164).	[22]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Sialomucin core protein 24 (CD164).	[23]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Sialomucin core protein 24 (CD164).	[24]
Diphenylpyraline	DMW4X37	Approved	Diphenylpyraline decreases the expression of Sialomucin core protein 24 (CD164).	[25]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Sialomucin core protein 24 (CD164).	[26]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Sialomucin core protein 24 (CD164).	[27]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine decreases the expression of Sialomucin core protein 24 (CD164).	[28]

References

• [1] Protective Effects of Chronic Intermittent Hypobaric Hypoxia Pretreatment against Aplastic Anemia through Improving the Adhesiveness and Stress of Mesenchymal Stem Cells in Rats.Stem Cells Int. 2017;2017:5706193. doi: 10.1155/2017/5706193. Epub 2017 Jul 16.
• [2] A novel core protein as well as polymorphic epithelial mucin carry peanut agglutinin binding sites in human gastric carcinoma cells: sequence analysis and examination of gene expression.J Biochem. 1992 Nov;112(5):609-15. doi: 10.1093/oxfordjournals.jbchem.a123948.
• [3] CD164 regulates proliferation, progression, and invasion of human glioblastoma cells.Oncotarget. 2019 Mar 12;10(21):2041-2054. doi: 10.18632/oncotarget.26724. eCollection 2019 Mar 12.
• [4] CD164 identifies CD4(+) T cells highly expressing genes associated with malignancy in Szary syndrome: the Szary signature genes, FCRL3, Tox, and miR-214.Arch Dermatol Res. 2017 Jan;309(1):11-19. doi: 10.1007/s00403-016-1698-8. Epub 2016 Oct 20.
• [5] CD164 promotes tumor progression and predicts the poor prognosis of bladder cancer.Cancer Med. 2018 Aug;7(8):3763-3772. doi: 10.1002/cam4.1607. Epub 2018 Jul 18.
• [6] A Novel Locus Harbouring a Functional CD164 Nonsense Mutation Identified in a Large Danish Family with Nonsyndromic Hearing Impairment. PLoS Genet. 2015 Jul 21;11(7):e1005386. doi: 10.1371/journal.pgen.1005386. eCollection 2015 Jul.
• [7] Overexpression of CD164 in oral cavity squamous cell carcinoma predicts a favourable prognosis.Oncol Lett. 2017 Nov;14(5):6103-6108. doi: 10.3892/ol.2017.6966. Epub 2017 Sep 15.
• [8] Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set of disease-associated genes and reveals the clinical significance of Wilms' tumor gene 1 (WT1).Stem Cells. 2007 Jan;25(1):165-73. doi: 10.1634/stemcells.2006-0351. Epub 2006 Sep 21.
• [9] Comparative transcriptional study of the effects of high intracellular zinc on prostate carcinoma cells.Oncol Rep. 2010 Jun;23(6):1501-16. doi: 10.3892/or_00000789.
• [10] The role of sialomucin CD164 (MGC-24v or endolyn) in prostate cancer metastasis.BMC Cancer. 2006 Jul 21;6:195. doi: 10.1186/1471-2407-6-195.
• [11] The ratio of splicing variants of MGC-24/CD164, a sialomucin, correlates with the metastatic potential of colorectal carcinomas.J Biochem. 2000 Jun;127(6):1103-7. doi: 10.1093/oxfordjournals.jbchem.a022704.
• [12] CD164 regulates the tumorigenesis of ovarian surface epithelial cells through the SDF-1/CXCR4 axis.Mol Cancer. 2013 Oct 5;12(1):115. doi: 10.1186/1476-4598-12-115.
• [13] CD164 promotes lung tumor-initiating cells with stem cell activity and determines tumor growth and drug resistance via Akt/mTOR signaling.Oncotarget. 2016 Aug 9;8(33):54115-54135. doi: 10.18632/oncotarget.11132. eCollection 2017 Aug 15.
• [14] 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.
• [15] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [16] 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.
• [17] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [18] Transcriptional responses to estrogen and progesterone in mammary gland identify networks regulating p53 activity. Endocrinology. 2008 Oct;149(10):4809-20. doi: 10.1210/en.2008-0035. Epub 2008 Jun 12.
• [19] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [20] Global effects of inorganic arsenic on gene expression profile in human macrophages. Mol Immunol. 2009 Feb;46(4):649-56.
• [21] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [22] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [23] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [24] The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils. Blood. 2008 Mar 15;111(6):3097-107.
• [25] Controlled diesel exhaust and allergen coexposure modulates microRNA and gene expression in humans: Effects on inflammatory lung markers. J Allergy Clin Immunol. 2016 Dec;138(6):1690-1700. doi: 10.1016/j.jaci.2016.02.038. Epub 2016 Apr 24.
• [26] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [27] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [28] Differential response of Mono Mac 6, BEAS-2B, and Jurkat cells to indoor dust. Environ Health Perspect. 2007 Sep;115(9):1325-32.