Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9A9Q1X)

• DOT Name: Layilin (LAYN)
• Gene Name: LAYN
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Chronic obstructive pulmonary disease
  Clear cell renal carcinoma
  Colitis
  Colon adenocarcinoma
  Colon cancer
  Gastric adenocarcinoma
  Gastric cancer
  Glomerulonephritis
  Inflammatory bowel disease
  Lung adenocarcinoma
  Lung carcinoma
  Malignant glioma
  Neoplasm
  Stomach cancer
  Osteoarthritis
• UniProt ID: LAYN_HUMAN
• Pfam ID: PF00059
• Sequence:
  MRPGTALQAVLLAVLLVGLRAATGRLLSASDLDLRGGQPVCRGGTQRPCYKVIYFHDTSR
  RLNFEEAKEACRRDGGQLVSIESEDEQKLIEKFIENLLPSDGDFWIGLRRREEKQSNSTA
  CQDLYAWTDGSISQFRNWYVDEPSCGSEVCVVMYHQPSAPAGIGGPYMFQWNDDRCNMKN
  NFICKYSDEKPAVPSREAEGEETELTTPVLPEETQEEDAKKTFKESREAALNLAYILIPS
  IPLLLLLVVTTVVCWVWICRKRKREQPDPSTKKQHTIWPSPHQGNSPDLEVYNVIRKQSE
  ADLAETRPDLKNISFRVCSGEATPDDMSCDYDNMAVNPSESGFVTLVSVESGFVTNDIYE
  FSPDQMGRSKESGWVENEIYGY
• Function: Receptor for hyaluronate.

Molecular Interaction Atlas (MIA) of This DOT

17 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Biomarker	[1]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[3]
Colitis	DISAF7DD	Strong	Biomarker	[4]
Colon adenocarcinoma	DISDRE0J	Strong	Altered Expression	[1]
Colon cancer	DISVC52G	Strong	Biomarker	[1]
Gastric adenocarcinoma	DISWWLTC	Strong	Biomarker	[1]
Gastric cancer	DISXGOUK	Strong	Altered Expression	[1]
Glomerulonephritis	DISPZIQ3	Strong	Altered Expression	[3]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[4]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[5]
Lung carcinoma	DISTR26C	Strong	Biomarker	[6]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Altered Expression	[1]
Stomach cancer	DISKIJSX	Strong	Altered Expression	[1]
Osteoarthritis	DIS05URM	Limited	Biomarker	[8]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Layilin (LAYN).	[9]

9 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 Layilin (LAYN).	[10]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Layilin (LAYN).	[11]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Layilin (LAYN).	[12]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Layilin (LAYN).	[13]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Layilin (LAYN).	[14]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Layilin (LAYN).	[15]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Layilin (LAYN).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Layilin (LAYN).	[16]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Layilin (LAYN).	[17]

References

• [1] LAYN Is a Prognostic Biomarker and Correlated With Immune Infiltrates in Gastric and Colon Cancers.Front Immunol. 2019 Jan 29;10:6. doi: 10.3389/fimmu.2019.00006. eCollection 2019.
• [2] Identification of prefrontal cortex protein alterations in Alzheimer's disease.Oncotarget. 2018 Jan 24;9(13):10847-10867. doi: 10.18632/oncotarget.24303. eCollection 2018 Feb 16.
• [3] Roles of layilin in TNF--induced epithelial-mesenchymal transformation of renal tubular epithelial cells.Biochem Biophys Res Commun. 2015 Nov 6;467(1):63-9. doi: 10.1016/j.bbrc.2015.09.121. Epub 2015 Sep 26.
• [4] Layilin is critical for mediating hyaluronan 35kDa-induced intestinal epithelial tight junction protein ZO-1 in vitro and in vivo.Matrix Biol. 2018 Mar;66:93-109. doi: 10.1016/j.matbio.2017.09.003. Epub 2017 Oct 1.
• [5] Genome-wide unmasking of epigenetically silenced genes in lung adenocarcinoma from smokers and never smokers.Carcinogenesis. 2014 Jun;35(6):1248-57. doi: 10.1093/carcin/bgt494. Epub 2014 Jan 7.
• [6] Down-regulation of layilin, a novel hyaluronan receptor, via RNA interference, inhibits invasion and lymphatic metastasis of human lung A549 cells.Biotechnol Appl Biochem. 2008 Jun;50(Pt 2):89-96. doi: 10.1042/BA20070138.
• [7] Layilin enhances the invasive ability of malignant glioma cells via SNAI1 signaling.Brain Res. 2019 Sep 15;1719:140-147. doi: 10.1016/j.brainres.2019.05.034. Epub 2019 May 27.
• [8] Anti-Inflammatory Effects of Intra-Articular Hyaluronic Acid: A Systematic Review.Cartilage. 2019 Jan;10(1):43-52. doi: 10.1177/1947603517749919. Epub 2018 Feb 11.
• [9] 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.
• [10] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [11] 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.
• [12] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [13] 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.
• [14] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [15] 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.
• [16] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [17] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.