Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQLH551)

• DOT Name: Pre-mRNA-splicing factor 38B (PRPF38B)
• Synonyms: Sarcoma antigen NY-SAR-27
• Gene Name: PRPF38B
• Related Disease:
  Carcinoma
  Cervical Intraepithelial neoplasia
  Dentin dysplasia
  Dentinogenesis imperfecta
  Hepatocellular carcinoma
  Herpes simplex infection
  Invasive breast carcinoma
  Invasive ductal breast carcinoma
  Non-small-cell lung cancer
  Cutaneous squamous cell carcinoma
  Gastric adenocarcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
• UniProt ID: PR38B_HUMAN
• Pfam ID: PF03371
• Sequence:
  MANNSPALTGNSQPQHQAAAAAAQQQQQCGGGGATKPAVSGKQGNVLPLWGNEKTMNLNP
  MILTNILSSPYFKVQLYELKTYHEVVDEIYFKVTHVEPWEKGSRKTAGQTGMCGGVRGVG
  TGGIVSTAFCLLYKLFTLKLTRKQVMGLITHTDSPYIRALGFMYIRYTQPPTDLWDWFES
  FLDDEEDLDVKAGGGCVMTIGEMLRSFLTKLEWFSTLFPRIPVPVQKNIDQQIKTRPRKI
  KKDGKEGAEEIDRHVERRRSRSPRRSLSPRRSPRRSRSRSHHREGHGSSSFDRELEREKE
  RQRLEREAKEREKERRRSRSIDRGLERRRSRSRERHRSRSRSRDRKGDRRDRDREREKEN
  ERGRRRDRDYDKERGNEREKERERSRERSKEQRSRGEVEEKKHKEDKDDRRHRDDKRDSK
  KEKKHSRSRSRERKHRSRSRSRNAGKRSRSRSKEKSSKHKNESKEKSNKRSRSGSQGRTD
  SVEKSKKREHSPSKEKSRKRSRSKERSHKRDHSDSKDQSDKHDRRRSQSIEQESQEKQHK
  NKDETV
• Function: May be required for pre-mRNA splicing.
• KEGG Pathway: Spliceosome (hsa03040)

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Carcinoma	DISH9F1N	Strong	Biomarker	[1]
Cervical Intraepithelial neoplasia	DISXP757	Strong	Altered Expression	[1]
Dentin dysplasia	DISCGIX8	Strong	Genetic Variation	[2]
Dentinogenesis imperfecta	DISJLZU4	Strong	Genetic Variation	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
Herpes simplex infection	DISL1SAV	Strong	Biomarker	[4]
Invasive breast carcinoma	DISANYTW	Strong	Altered Expression	[5]
Invasive ductal breast carcinoma	DIS43J58	Strong	Altered Expression	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[6]
Cutaneous squamous cell carcinoma	DIS3LXUG	moderate	Biomarker	[7]
Gastric adenocarcinoma	DISWWLTC	moderate	Biomarker	[8]
Advanced cancer	DISAT1Z9	Limited	Altered Expression	[7]
Breast cancer	DIS7DPX1	Limited	Biomarker	[5]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Pre-mRNA-splicing factor 38B (PRPF38B).	[9]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Pre-mRNA-splicing factor 38B (PRPF38B).	[10]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Pre-mRNA-splicing factor 38B (PRPF38B).	[11]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Pre-mRNA-splicing factor 38B (PRPF38B).	[13]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Pre-mRNA-splicing factor 38B (PRPF38B).	[14]

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 increases the methylation of Pre-mRNA-splicing factor 38B (PRPF38B).	[12]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the phosphorylation of Pre-mRNA-splicing factor 38B (PRPF38B).	[15]

References

• [1] Identification of a new proliferation-associated protein NET-1/C4.8 characteristic for a subset of high-grade cervical intraepithelial neoplasia and cervical carcinomas.Int J Cancer. 2002 Jun 20;99(6):771-5. doi: 10.1002/ijc.10442.
• [2] Overlapping DSPP mutations cause dentin dysplasia and dentinogenesis imperfecta.J Dent Res. 2008 Dec;87(12):1108-11. doi: 10.1177/154405910808701217.
• [3] Inhibition of NET-1 suppresses proliferation and promotes apoptosis of hepatocellular carcinoma cells by activating the PI3K/AKT signaling pathway.Exp Ther Med. 2019 Mar;17(3):2334-2340. doi: 10.3892/etm.2019.7211. Epub 2019 Jan 29.
• [4] A net +1 frameshift permits synthesis of thymidine kinase from a drug-resistant herpes simplex virus mutant.Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5461-5. doi: 10.1073/pnas.91.12.5461.
• [5] The localization of pre mRNA splicing factor PRPF38B is a novel prognostic biomarker that may predict survival benefit of trastuzumab in patients with breast cancer overexpressing HER2.Oncotarget. 2017 Nov 18;8(68):112245-112257. doi: 10.18632/oncotarget.22496. eCollection 2017 Dec 22.
• [6] Neuroepithelial transforming gene 1 functions as a potential prognostic marker for patients with non-small cell lung cancer.Mol Med Rep. 2015 Nov;12(5):7439-46. doi: 10.3892/mmr.2015.4385. Epub 2015 Sep 29.
• [7] Inhibition of skin squamous cell carcinoma proliferation and promote apoptosis by dual silencing of NET-1 and survivin.Oncol Rep. 2015 Aug;34(2):811-22. doi: 10.3892/or.2015.4062. Epub 2015 Jun 15.
• [8] Net1 and Myeov: computationally identified mediators of gastric cancer.Br J Cancer. 2006 Apr 24;94(8):1204-12. doi: 10.1038/sj.bjc.6603054.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [11] Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells. Brain Res. 2006 Oct 20;1116(1):39-49.
• [12] 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.
• [13] 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.
• [14] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [15] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.