Details of Drug Off-Target (DOT)

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

• DOT Name: High mobility group nucleosome-binding domain-containing protein 5 (HMGN5)
• Synonyms: Nucleosome-binding protein 1
• Gene Name: HMGN5
• Related Disease:
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Endometrium adenocarcinoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Glioma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Osteosarcoma
  Prostate cancer
  Squamous cell carcinoma
  Stomach cancer
  Bladder transitional cell carcinoma
  Meningioma
  Renal cell carcinoma
  Malignant glioma
  Matthew-Wood syndrome
  Mixed glioma
  Pancreatic ductal carcinoma
  Prostate carcinoma
  Prostate neoplasm
• UniProt ID: HMGN5_HUMAN
• Pfam ID: PF01101
• Sequence:
  MPKRKAAGQGDMRQEPKRRSARLSAMLVPVTPEVKPKRTSSSRKMKTKSDMMEENIDTSA
  QAVAETKQEAVVEEDYNENAKNGEAKITEAPASEKEIVEVKEENIEDATEKGGEKKEAVA
  AEVKNEEEDQKEDEEDQNEEKGEAGKEDKDEKGEEDGKEDKNGNEKGEDAKEKEDGKKGE
  DGKGNGEDGKEKGEDEKEEEDRKETGDGKENEDGKEKGDKKEGKDVKVKEDEKEREDGKE
  DEGGNEEEAGKEKEDLKEEEEGKEEDEIKEDDGKKEEPQSIV
• Function: Preferentially binds to euchromatin and modulates cellular transcription by counteracting linker histone-mediated chromatin compaction.
• Tissue Specificity: Ubiquitously expressed.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Biomarker	[2]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[2]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[3]
Endometrium adenocarcinoma	DISY6744	Strong	Altered Expression	[4]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	Strong	Biomarker	[6]
Glioma	DIS5RPEH	Strong	Altered Expression	[7]
Lung cancer	DISCM4YA	Strong	Altered Expression	[8]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[8]
Neoplasm	DISZKGEW	Strong	Altered Expression	[6]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[9]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[1]
Prostate cancer	DISF190Y	Strong	Biomarker	[10]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[6]
Bladder transitional cell carcinoma	DISNL46A	moderate	Altered Expression	[11]
Meningioma	DISPT4TG	moderate	Biomarker	[12]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[3]
Malignant glioma	DISFXKOV	Limited	Biomarker	[13]
Matthew-Wood syndrome	DISA7HR7	Limited	Biomarker	[14]
Mixed glioma	DIS64UY3	Limited	Biomarker	[13]
Pancreatic ductal carcinoma	DIS26F9Q	Limited	Altered Expression	[14]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[10]
Prostate neoplasm	DISHDKGQ	Limited	Biomarker	[13]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	High mobility group nucleosome-binding domain-containing protein 5 (HMGN5) decreases the response to substance of Cisplatin.	[5]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[24]
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[16]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[17]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[18]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[19]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[20]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[21]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[22]
Rifampicin	DM5DSFZ	Approved	Rifampicin increases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[20]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of High mobility group nucleosome-binding domain-containing protein 5 (HMGN5).	[26]

References

• [1] MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy.Sci Rep. 2017 Mar 24;7(1):416. doi: 10.1038/s41598-017-00405-3.
• [2] The high-mobility group nucleosome-binding domain 5 is highly expressed in breast cancer and promotes the proliferation and invasion of breast cancer cells.Tumour Biol. 2015 Feb;36(2):959-66. doi: 10.1007/s13277-014-2715-1. Epub 2014 Oct 15.
• [3] miR-488 inhibits cell growth and metastasis in renal cell carcinoma by targeting HMGN5.Onco Targets Ther. 2018 Apr 18;11:2205-2216. doi: 10.2147/OTT.S156361. eCollection 2018.
• [4] HMGN5: a potential oncogene in gliomas.J Neurooncol. 2011 Sep;104(3):729-36. doi: 10.1007/s11060-011-0558-9. Epub 2011 Mar 4.
• [5] Silencing HMGN5 suppresses cell growth and promotes chemosensitivity in esophageal squamous cell carcinoma. J Biochem Mol Toxicol. 2017 Dec;31(12). doi: 10.1002/jbt.21996. Epub 2017 Sep 15.
• [6] The nucleosome binding protein 1 promotes the growth of gastric cancer cells.J Cancer. 2019 Jan 29;10(5):1132-1137. doi: 10.7150/jca.29292. eCollection 2019.
• [7] MicroRNA-409-3p Represses Glioma Cell Invasion and Proliferation by Targeting High-Mobility Group Nucleosome-Binding Domain 5.Oncol Res. 2017 Aug 7;25(7):1097-1107. doi: 10.3727/096504017X14836170586829. Epub 2017 Jan 20.
• [8] Knockdown of HMGN5 expression by RNA interference induces cell cycle arrest in human lung cancer cells.Asian Pac J Cancer Prev. 2012;13(7):3223-8. doi: 10.7314/apjcp.2012.13.7.3223.
• [9] Suppression of nucleosome-binding protein 1 by miR-326 impedes cell proliferation and invasion in non-small cell lung cancer cells.Oncol Rep. 2016 Feb;35(2):1117-24. doi: 10.3892/or.2015.4403. Epub 2015 Nov 6.
• [10] microRNA-183-3p Inhibits Progression of Human Prostate Cancer by Downregulating High-Mobility Group Nucleosome Binding Domain 5.DNA Cell Biol. 2019 Aug;38(8):840-848. doi: 10.1089/dna.2019.4642. Epub 2019 Jul 17.
• [11] HMGN5 expression in bladder cancer tissue and its role on prognosis.Eur Rev Med Pharmacol Sci. 2018 Feb;22(4):970-975. doi: 10.26355/eurrev_201802_14378.
• [12] HMGN5 blockade by siRNA enhances apoptosis, suppresses invasion and increases chemosensitivity to temozolomide in meningiomas.Int J Oncol. 2015 Oct;47(4):1503-11. doi: 10.3892/ijo.2015.3131. Epub 2015 Aug 25.
• [13] Neonatal exposure to estradiol/bisphenol A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in the rat prostate gland throughout life.Endocrinology. 2012 Jan;153(1):42-55. doi: 10.1210/en.2011-1308. Epub 2011 Nov 22.
• [14] HMGN5 promotes proliferation and invasion via the activation of Wnt/-catenin signaling pathway in pancreatic ductal adenocarcinoma.Oncol Lett. 2018 Sep;16(3):4013-4019. doi: 10.3892/ol.2018.9090. Epub 2018 Jul 5.
• [15] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [16] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [17] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [18] 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.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [21] Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 2006 Mar 1;66(5):2765-77.
• [22] 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.
• [23] Integrated analysis of rifampicin-induced microRNA and gene expression changes in human hepatocytes. Drug Metab Pharmacokinet. 2014;29(4):333-40.
• [24] 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.
• [25] Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
• [26] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.
• [27] Silencing HMGN5 suppresses cell growth and promotes chemosensitivity in esophageal squamous cell carcinoma. J Biochem Mol Toxicol. 2017 Dec;31(12). doi: 10.1002/jbt.21996. Epub 2017 Sep 15.