Details of Drug Off-Target (DOT)

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

• DOT Name: Cornifelin (CNFN)
• Gene Name: CNFN
• Related Disease:
  Head and neck cancer
  Head and neck carcinoma
• UniProt ID: CNFN_HUMAN
• Pfam ID: PF04749
• Sequence:
  MSYPVTSQPQCATTSCYQTQLSDWHTGLTDCCNDMPVCLCGTFAPLCLACRISDDFGECC
  CAPYLPGGLHSIRTGMRERYHIQGSVGHDWAALTFCLPCALCQMARELKIRE
• Function: Part of the insoluble cornified cell envelope (CE) of stratified squamous epithelia.
• Tissue Specificity: Abundant in the cervix. Moderately abundant in the uterus and fetal skin. Expression is markedly increased in psoriatic skin (18.5 fold increase in comparison with normal skin) and its overexpression alters the protein composition of cornified cell envelope (CE), but does not affect keratinocyte differentiation. Expressed in the granular cell layer of epidermis in uninvolved psoriatic skin and in the psoriatic lesions it is found in the upper-spinous layer. Increased expression also seen in atopic dermatitis (14.3 fold increase in comparison with normal skin) and mycosis fungoides (4.6 fold increase in comparison with normal skin) and in both conditions expressed in the granular cell layer of epidermis.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[1]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[1]

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 Cornifelin (CNFN).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cornifelin (CNFN).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cornifelin (CNFN).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cornifelin (CNFN).	[4]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Cornifelin (CNFN).	[5]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate increases the expression of Cornifelin (CNFN).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cornifelin (CNFN).	[7]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Cornifelin (CNFN).	[8]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Cornifelin (CNFN).	[10]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Cornifelin (CNFN).	[11]

References

• [1] Analysis of gene coexpression network reveals prognostic significance of CNFN in patients with head and neck cancer.Oncol Rep. 2019 Apr;41(4):2168-2180. doi: 10.3892/or.2019.7019. Epub 2019 Feb 18.
• [2] 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.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [6] Identification of cornifelin and early growth response-1 gene as novel biomarkers for in vitro eye irritation using a 3D reconstructed human cornea model MCTT HCE?. Arch Toxicol. 2015 Sep;89(9):1589-98. doi: 10.1007/s00204-014-1390-8. Epub 2014 Nov 7.
• [7] 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.
• [8] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [9] 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.
• [10] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [11] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.