Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2MR6O2)

• DOT Name: U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25)
• Synonyms: U11/U12 snRNP 25 kDa protein; U11/U12-25K; Minus-99 protein
• Gene Name: SNRNP25
• Related Disease:
  Bone osteosarcoma
  Osteosarcoma
  Neoplasm
• UniProt ID: SNR25_HUMAN
• Pfam ID: PF18036
• Sequence:
  MDVFQEGLAMVVQDPLLCDLPIQVTLEEVNSQIALEYGQAMTVRVCKMDGEVMPVVVVQS
  ATVLDLKKAIQRYVQLKQEREGGIQHISWSYVWRTYHLTSAGEKLTEDRKKLRDYGIRNR
  DEVSFIKKLRQK
• Reactome Pathway: mRNA Splicing - Minor Pathway (R-HSA-72165)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Strong	Biomarker	[1]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[1]
Neoplasm	DISZKGEW	moderate	Biomarker	[2]

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25) affects the response to substance of Paclitaxel.	[13]
Vinblastine	DM5TVS3	Approved	U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25) affects the response to substance of Vinblastine.	[13]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[3]

9 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 U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[11]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of U11/U12 small nuclear ribonucleoprotein 25 kDa protein (SNRNP25).	[12]

References

• [1] Roles of low-density lipoprotein receptor-related protein 1 in tumors.Chin J Cancer. 2016 Jan 6;35:6. doi: 10.1186/s40880-015-0064-0.
• [2] Recurrent LRP1-SNRNP25 and KCNMB4-CCND3 fusion genes promote tumor cell motility in human osteosarcoma.J Hematol Oncol. 2014 Oct 10;7:76. doi: 10.1186/s13045-014-0076-2.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] 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.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [13] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.