Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGDPS5C)

• DOT Name: Host cell factor C1 regulator 1 (HCFC1R1)
• Synonyms: HCF-1 beta-propeller-interacting protein
• Gene Name: HCFC1R1
• Related Disease:
  Advanced cancer
  Lung cancer
  Lung carcinoma
  Cervical cancer
  Cervical carcinoma
  Epithelial ovarian cancer
  Head-neck squamous cell carcinoma
  Neoplasm
  Ovarian cancer
  Ovarian neoplasm
  Hepatocellular carcinoma
• UniProt ID: HPIP_HUMAN
• Pfam ID: PF15226
• Sequence:
  MILQQPLQRGPQGGAQRLPRAALGVTWGLDASSPLRGAVPMSTKRRLEEEQEPLRKQFLS
  EENMATHFSQLSLHNDHPYCSPPMTFSPALPPLRSPCSELLLWRYPGSLIPEALRLLRLG
  DTPSPPYPATPAGDIMEL
• Function: Regulates HCFC1 activity by modulating its subcellular localization. Overexpression of HCFC1R1 leads to accumulation of HCFC1 in the cytoplasm. HCFC1R1-mediated export may provide the pool of cytoplasmic HCFC1 required for import of virion-derived VP16 into the nucleus.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Lung carcinoma	DISTR26C	Definitive	Altered Expression	[1]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[2]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[2]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[3]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[4]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[3]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[3]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[5]

16 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 Host cell factor C1 regulator 1 (HCFC1R1).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[8]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[10]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[11]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[12]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[13]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[14]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[15]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[10]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[16]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[17]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[18]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Host cell factor C1 regulator 1 (HCFC1R1).	[20]

References

• [1] HPIP silencing inhibits TGF-1-induced EMT in lung cancer cells.Int J Mol Med. 2017 Feb;39(2):479-483. doi: 10.3892/ijmm.2017.2851. Epub 2017 Jan 5.
• [2] Expression and clinicopathological significance of hematopoietic pre-B cell leukemia transcription factor-interacting protein in cervical carcinoma.Pathol Res Pract. 2018 Sep;214(9):1340-1344. doi: 10.1016/j.prp.2017.07.031. Epub 2017 Aug 1.
• [3] HPIP Silencing Prevents Epithelial-Mesenchymal Transition Induced by TGF-1 in Human Ovarian Cancer Cells.Oncol Res. 2016;24(1):33-9. doi: 10.3727/096504016X14575597858654.
• [4] Knockdown of HPIP Inhibits the Proliferation and Invasion of Head-and-Neck Squamous Cell Carcinoma Cells by Regulating PI3K/Akt Signaling Pathway.Oncol Res. 2016;24(3):153-60. doi: 10.3727/096504016X14612603423476.
• [5] CSR1 suppresses tumor growth and metastasis of human hepatocellular carcinoma via inhibition of HPIP.Eur Rev Med Pharmacol Sci. 2017 Oct;21(17):3813-3820.
• [6] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [7] 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.
• [8] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [11] 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.
• [12] 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.
• [13] 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.
• [14] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [15] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [16] 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.
• [17] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [18] 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.
• [19] The molecular basis of genistein-induced mitotic arrest and exit of self-renewal in embryonal carcinoma and primary cancer cell lines. BMC Med Genomics. 2008 Oct 10;1:49.
• [20] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.