Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTFTT6VN)

• DOT Name: Leucine-rich repeat-containing protein 28 (LRRC28)
• Gene Name: LRRC28
• Related Disease:
  Colorectal carcinoma
  Hepatocellular carcinoma
• UniProt ID: LRC28_HUMAN
• Pfam ID: PF13855
• Sequence:
  MASELCKTISVARLEKHKNLFLNYRNLHHFPLELLKDEGLQYLERLYMKRNSLTSLPENL
  AQKLPNLVELYLHSNNIVVVPEAIGSLVKLQCLDLSDNALEIVCPEIGRLRALRHLRLAN
  NQLQFLPPEVGDLKELQTLDISTNRLLTLPERLHMCLSLQYLTVDRNRLWYVPRHLCQLP
  SLNELSMAGNRLAFLPLDLGRSRELQYVYVDNNIHLKGLPSYLYNKVIGCSGCGAPIQVS
  EVKLLSFSSGQRTVFLPAEVKAIGTEHDHVLPLQELAMRGLYHTYHSLLKDLNFLSPISL
  PRSLLELLHCPLGHCHRCSEPMFTIVYPKLFPLRETPMAGLHQWKTTVSFVAYCCSTQCL
  QTFDLLS

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colorectal carcinoma	DIS5PYL0	Definitive	Altered Expression	[1]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[9]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[10]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[11]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[12]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Leucine-rich repeat-containing protein 28 (LRRC28).	[14]

References

• [1] The expression of leucine-rich repeat gene family members in colorectal cancer.Exp Biol Med (Maywood). 2012 Oct;237(10):1123-8. doi: 10.1258/ebm.2012.012042. Epub 2012 Oct 8.
• [2] Identification of differential expression of genes in hepatocellular carcinoma by suppression subtractive hybridization combined cDNA microarray.Oncol Rep. 2007 Oct;18(4):943-51.
• [3] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [11] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [12] Differentially expressed genes in the prostate cancer cell line LNCaP after exposure to androgen and anti-androgen. Cancer Genet Cytogenet. 2006 Apr 15;166(2):130-8. doi: 10.1016/j.cancergencyto.2005.09.012.
• [13] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [14] 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.