Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYS6WQ8)

• DOT Name: Paraspeckle component 1 (PSPC1)
• Synonyms: Paraspeckle protein 1
• Gene Name: PSPC1
• Related Disease:
  Neoplasm
  Advanced cancer
  Obesity
  Progressive supranuclear palsy
  Colorectal carcinoma
  Hepatocellular carcinoma
• UniProt ID: PSPC1_HUMAN
• PDB ID: 3SDE; 5IFN; 5WPA
• Pfam ID: PF08075 ; PF00076
• Sequence:
  MMLRGNLKQVRIEKNPARLRALESAVGESEPAAAAAMALALAGEPAPPAPAPPEDHPDEE
  MGFTIDIKSFLKPGEKTYTQRCRLFVGNLPTDITEEDFKRLFERYGEPSEVFINRDRGFG
  FIRLESRTLAEIAKAELDGTILKSRPLRIRFATHGAALTVKNLSPVVSNELLEQAFSQFG
  PVEKAVVVVDDRGRATGKGFVEFAAKPPARKALERCGDGAFLLTTTPRPVIVEPMEQFDD
  EDGLPEKLMQKTQQYHKEREQPPRFAQPGTFEFEYASRWKALDEMEKQQREQVDRNIREA
  KEKLEAEMEAARHEHQLMLMRQDLMRRQEELRRLEELRNQELQKRKQIQLRHEEEHRRRE
  EEMIRHREQEELRRQQEGFKPNYMENREQEMRMGDMGPRGAINMGDAFSPAPAGNQGPPP
  MMGMNMNNRATIPGPPMGPGPAMGPEGAANMGTPMMPDNGAVHNDRFPQGPPSQMGSPMG
  SRTGSETPQAPMSGVGPVSGGPGGFGRGSQGGNFEGPNKRRRY
• Function: Regulates, cooperatively with NONO and SFPQ, androgen receptor-mediated gene transcription activity in Sertoli cell line. Binds to poly(A), poly(G) and poly(U) RNA homopolymers. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer. Together with NONO, required for the formation of nuclear paraspeckles. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.
• Tissue Specificity: Expressed in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain and heart.

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neoplasm	DISZKGEW	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[3]
Progressive supranuclear palsy	DISO5KRQ	Strong	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Limited	Biomarker	[6]

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 Paraspeckle component 1 (PSPC1).	[7]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Paraspeckle component 1 (PSPC1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Paraspeckle component 1 (PSPC1).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Paraspeckle component 1 (PSPC1).	[10]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Paraspeckle component 1 (PSPC1).	[11]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Paraspeckle component 1 (PSPC1).	[12]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Paraspeckle component 1 (PSPC1).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Paraspeckle component 1 (PSPC1).	[14]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Paraspeckle component 1 (PSPC1).	[15]
Progesterone	DMUY35B	Approved	Progesterone decreases the expression of Paraspeckle component 1 (PSPC1).	[16]
Cidofovir	DMA13GD	Approved	Cidofovir decreases the expression of Paraspeckle component 1 (PSPC1).	[17]
Ifosfamide	DMCT3I8	Approved	Ifosfamide decreases the expression of Paraspeckle component 1 (PSPC1).	[17]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Paraspeckle component 1 (PSPC1).	[17]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Paraspeckle component 1 (PSPC1).	[18]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Paraspeckle component 1 (PSPC1).	[19]

References

• [1] PSPC1 mediates TGF-1 autocrine signalling and Smad2/3 target switching to promote EMT, stemness and metastasis.Nat Cell Biol. 2018 Apr;20(4):479-491. doi: 10.1038/s41556-018-0062-y. Epub 2018 Mar 28.
• [2] PSPC1-interchanged interactions with PTK6 and -catenin synergize oncogenic subcellular translocations and tumor progression.Nat Commun. 2019 Dec 16;10(1):5716. doi: 10.1038/s41467-019-13665-6.
• [3] RNA-binding protein PSPC1 promotes the differentiation-dependent nuclear export of adipocyte RNAs.J Clin Invest. 2017 Mar 1;127(3):987-1004. doi: 10.1172/JCI89484. Epub 2017 Feb 13.
• [4] Similarities between familial and sporadic autopsy-proven progressive supranuclear palsy.Neurology. 2013 May 28;80(22):2076-8. doi: 10.1212/WNL.0b013e318294b2eb. Epub 2013 May 1.
• [5] Two precision medicine predictive tools for six malignant solid tumors: from gene-based research to clinical application.J Transl Med. 2019 Dec 3;17(1):405. doi: 10.1186/s12967-019-02151-8.
• [6] Hepatocellular Carcinoma and Nuclear Paraspeckles: Induction in Chemoresistance and Prediction for Poor Survival.Cell Physiol Biochem. 2019;52(4):787-801. doi: 10.33594/000000055.
• [7] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [8] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Nuclear proteome analysis of cisplatin-treated HeLa cells. Mutat Res. 2010 Sep 10;691(1-2):1-8. doi: 10.1016/j.mrfmmm.2010.06.002. Epub 2010 Jun 9.
• [12] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [13] 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.
• [14] 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.
• [15] Proteomic and functional analyses reveal a dual molecular mechanism underlying arsenic-induced apoptosis in human multiple myeloma cells. J Proteome Res. 2009 Jun;8(6):3006-19.
• [16] Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids. 2008 Jan;73(1):116-28.
• [17] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [18] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.