Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTE4I83Q)

• DOT Name: Cystatin-SN (CST1)
• Synonyms: Cystain-SA-I; Cystatin-1; Salivary cystatin-SA-1
• Gene Name: CST1
• Related Disease:
  Asthma
  Breast cancer
  Breast carcinoma
  Hepatocellular carcinoma
  Allergic rhinitis
  Bacterial vaginosis
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Craniosynostosis
  Esophageal squamous cell carcinoma
  Lung adenocarcinoma
  Nasal polyp
  Neoplasm
  Non-small-cell lung cancer
  Pancreatic cancer
  Pancreatic tumour
  Prostate cancer
  Prostate neoplasm
  Seasonal allergic rhinitis
  Stomach cancer
  Gastric neoplasm
  Hereditary diffuse gastric adenocarcinoma
  Gastric cancer
  Metastatic malignant neoplasm
  Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation
• UniProt ID: CYTN_HUMAN
• Pfam ID: PF00031
• Sequence:
  MAQYLSTLLLLLATLAVALAWSPKEEDRIIPGGIYNADLNDEWVQRALHFAISEYNKATK
  DDYYRRPLRVLRARQQTVGGVNYFFDVEVGRTICTKSQPNLDTCAFHEQPELQKKQLCSF
  EIYEVPWENRRSLVKSRCQES
• Function: Human saliva appears to contain several cysteine proteinase inhibitors that are immunologically related to cystatin S but that differ in their specificity due to amino acid sequence differences. Cystatin SN, with a pI of 7.5, is a much better inhibitor of papain and dipeptidyl peptidase I than is cystatin S, although both inhibit ficin equally well.
• Tissue Specificity: Expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). Expressed in saliva, tears, urine and seminal fluid.
• KEGG Pathway: Salivary secretion (hsa04970)

Molecular Interaction Atlas (MIA) of This DOT

26 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Asthma	DISW9QNS	Definitive	Altered Expression	[1]
Breast cancer	DIS7DPX1	Definitive	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Definitive	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Definitive	Biomarker	[3]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[4]
Bacterial vaginosis	DISK2MZ2	Strong	Biomarker	[5]
Colon cancer	DISVC52G	Strong	Altered Expression	[6]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[6]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Craniosynostosis	DIS6J405	Strong	Biomarker	[7]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Altered Expression	[8]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[9]
Nasal polyp	DISLP3XE	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[3]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[10]
Pancreatic cancer	DISJC981	Strong	Altered Expression	[11]
Pancreatic tumour	DIS3U0LK	Strong	Biomarker	[11]
Prostate cancer	DISF190Y	Strong	Biomarker	[12]
Prostate neoplasm	DISHDKGQ	Strong	Biomarker	[12]
Seasonal allergic rhinitis	DIS58KQX	Strong	Biomarker	[13]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[14]
Gastric neoplasm	DISOKN4Y	moderate	Biomarker	[14]
Hereditary diffuse gastric adenocarcinoma	DISUIBYS	moderate	Biomarker	[14]
Gastric cancer	DISXGOUK	Limited	Biomarker	[14]
Metastatic malignant neoplasm	DIS86UK6	Limited	Altered Expression	[15]
Obsolete male infertility with azoospermia or oligozoospermia due to single gene mutation	DIS56JR8	Limited	Autosomal recessive	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Cystatin-SN (CST1) affects the response to substance of Methotrexate.	[22]
Etoposide	DMNH3PG	Approved	Cystatin-SN (CST1) affects the response to substance of Etoposide.	[22]

2 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 Cystatin-SN (CST1).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cystatin-SN (CST1).	[20]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cystatin-SN (CST1).	[18]
Lucanthone	DMZLBUO	Approved	Lucanthone increases the expression of Cystatin-SN (CST1).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Cystatin-SN (CST1).	[21]

References

• [1] Epithelium-derived cystatin SN enhances eosinophil activation and infiltration through IL-5 in patients with chronic rhinosinusitis with nasal polyps.J Allergy Clin Immunol. 2019 Aug;144(2):455-469. doi: 10.1016/j.jaci.2019.03.026. Epub 2019 Apr 8.
• [2] Correction to: Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis.J Mol Med (Berl). 2019 Aug;97(8):1213-1214. doi: 10.1007/s00109-019-01806-9.
• [3] Upregulation of cystatin SN promotes hepatocellular carcinoma progression and predicts a poor prognosis.J Cell Physiol. 2019 Dec;234(12):22623-22634. doi: 10.1002/jcp.28828. Epub 2019 May 20.
• [4] Human cystatin SN is an endogenous protease inhibitor that prevents allergic rhinitis.J Allergy Clin Immunol. 2019 Mar;143(3):1153-1162.e12. doi: 10.1016/j.jaci.2018.06.035. Epub 2018 Aug 23.
• [5] Factors associated with the composition and diversity of the cervical microbiota of reproductive-age Black South African women: a retrospective cross-sectional study.PeerJ. 2019 Aug 15;7:e7488. doi: 10.7717/peerj.7488. eCollection 2019.
• [6] Let?d inhibits colorectal cancer cell proliferation through the CST1/p65 pathway.Int J Oncol. 2018 Aug;53(2):781-790. doi: 10.3892/ijo.2018.4419. Epub 2018 May 23.
• [7] Expression and Functional Analysis of CST1 in Intractable Nasal Polyps.Am J Respir Cell Mol Biol. 2018 Oct;59(4):448-457. doi: 10.1165/rcmb.2017-0325OC.
• [8] Research progress of cystatin SN in cancer.Onco Targets Ther. 2019 May 6;12:3411-3419. doi: 10.2147/OTT.S194332. eCollection 2019.
• [9] Integrated analysis reveals candidate genes and transcription factors in lung adenocarcinoma.Mol Med Rep. 2017 Dec;16(6):8371-8379. doi: 10.3892/mmr.2017.7656. Epub 2017 Sep 28.
• [10] Expression of Cystatin SN significantly correlates with recurrence, metastasis, and survival duration in surgically resected non-small cell lung cancer patients.Sci Rep. 2015 Feb 4;5:8230. doi: 10.1038/srep08230.
• [11] Identification of cystatin SN as a novel biomarker for pancreatic cancer.Tumour Biol. 2015 May;36(5):3903-10. doi: 10.1007/s13277-014-3033-3. Epub 2015 Jan 12.
• [12] Microarray comparison of prostate tumor gene expression in African-American and Caucasian American males: a pilot project study.Infect Agent Cancer. 2009 Feb 10;4 Suppl 1(Suppl 1):S3. doi: 10.1186/1750-9378-4-S1-S3.
• [13] Epithelial proteome profiling suggests the essential role of interferon-inducible proteins in patients with allergic rhinitis.J Allergy Clin Immunol. 2017 Nov;140(5):1288-1298. doi: 10.1016/j.jaci.2017.05.040. Epub 2017 Jun 19.
• [14] Upregulation of the cysteine protease inhibitor, cystatin SN, contributes to cell proliferation and cathepsin inhibition in gastric cancer.Clin Chim Acta. 2009 Aug;406(1-2):45-51. doi: 10.1016/j.cca.2009.05.008. Epub 2009 May 19.
• [15] Cystatin SN inhibits auranofin-induced cell death by autophagic induction and ROS regulation via glutathione reductase activity in colorectal cancer.Cell Death Dis. 2017 Mar 16;8(3):e2682. doi: 10.1038/cddis.2017.100.
• [16] A genomics approach to male infertility. Genet Med. 2020 Dec;22(12):1967-1975. doi: 10.1038/s41436-020-0916-0. Epub 2020 Jul 28.
• [17] 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.
• [18] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [19] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [20] 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.
• [21] 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.
• [22] 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.