Details of Drug Off-Target (DOT)

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

DOT Name	Deleted in lung and esophageal cancer protein 1 (DLEC1)
Synonyms	Deleted in lung cancer protein 1; DLC-1
Gene Name	DLEC1
Related Disease	Esophageal squamous cell carcinoma ( ) Ovarian neoplasm ( ) Prostate cancer ( ) Adenoma ( ) Advanced cancer ( ) Allergic rhinitis ( ) Arteriosclerosis ( ) Atherosclerosis ( ) Breast neoplasm ( ) Burkitt lymphoma ( ) Cholangiocarcinoma ( ) Classic Hodgkin lymphoma ( ) Clear cell renal carcinoma ( ) Colorectal carcinoma ( ) Epithelial ovarian cancer ( ) Esophageal cancer ( ) Head-neck squamous cell carcinoma ( ) Hepatocellular carcinoma ( ) Intrahepatic cholangiocarcinoma ( ) Lung cancer ( ) Medulloblastoma ( ) Melanoma ( ) Metastatic malignant neoplasm ( ) Non-hodgkin lymphoma ( ) Non-small-cell lung cancer ( ) Plasma cell myeloma ( ) Renal carcinoma ( ) Renal cell carcinoma ( ) Squamous cell carcinoma ( ) Stomach cancer ( ) T-cell lymphoma ( ) Adult lymphoma ( ) Breast carcinoma ( ) Lymphoma ( ) Pancreatic cancer ( ) Pancreatic ductal carcinoma ( ) Pediatric lymphoma ( ) Benign prostatic hyperplasia ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Colon cancer ( ) Colon carcinoma ( ) Gastric cancer ( ) Kidney cancer ( ) Leiomyoma ( ) Liver cancer ( ) Prostate carcinoma ( ) Prostate neoplasm ( ) Uterine fibroids ( )
UniProt ID	DLEC1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Sequence	METRSSKTRRSLASRTNECQGTMWAPTSPPAGSSSPSQPTWKSSLYSSLAYSEAFHYSFA ARPRRLTQLALAQRPEPQLLRLRPSSLRTQDISHLLTGVFRNLYSAEVIGDEVSASLIKA RGSENERHEEFVDQLQQIRELYKQRLDEFEMLERHITQAQARAIAENERVMSQAGVQDLE SLVRLPPVKSVSRWCIDSELLRKHHLISPEDYYTDTVPFHSAPKGISLPGCSKLTFSCEK RSVQKKELNKKLEDSCRKKLAEFEDELDHTVDSLTWNLTPKAKERTREPLKKASQPRNKN WMNHLRVPQRELDRLLLARMESRNHFLKNPRFFPPNTRYGGKSLVFPPKKPAPIGEFQST EPEQSCADTPVFLAKPPIGFFTDYEIGPVYEMVIALQNTTTTSRYLRVLPPSTPYFALGL GMFPGKGGMVAPGMTCQYIVQFFPDCLGDFDDFILVETQSAHTLLIPLQARRPPPVLTLS PVLDCGYCLIGGVKMTRFICKNVGFSVGRFCIMPKTSWPPLSFKAIATVGFVEQPPFGIL PSVFELAPGHAILVEVLFSPKSLGKAEQTFIIMCDNCQIKELVTIGIGQLIALDLIYISG EKSQPDPGELTDLTAQHFIRFEPENLRSTARKQLIIRNATHVELAFYWQIMKPNLQPLMP GETFSMDSIKCYPDKETAFSIMPRKGVLSPHTDHEFILSFSPHELRDFHSVLQMVLEEVP EPVSSEAESLGHSSYSVDDVIVLEIEVKGSVEPFQVLLEPYALIIPGENYIGINVKKAFK MWNNSKSPIRYLWGKISDCHIIEVEPGTGVIEPSEVGDFELNFTGGVPGPTSQDLLCEIE DSPSPVVLHIEAVFKGPALIINVSALQFGLLRLGQKATNSIQIRNVSQLPATWRMKESPV SLQERPEDVSPFDIEPSSGQLHSLGECRVDITLEALHCQHLETVLELEVENGAWSYLPVY AEVQKPHVYLQSSQVEVRNLYLGVPTKTTITLINGTLLPTQFHWGKLLGHQAEFCMVTVS PKHGLLGPSEECQLKLELTAHTQEELTHLALPCHVSGMKKPLVLGISGKPQGLQVAITIS KESSDCSTEQWPGHPKELRLDFGSAVPLRTRVTRQLILTNRSPIRTRFSLKFEYFGSPQN SLSKKTSLPNMPPALLKTVRMQEHLAKREQLDFMESMLSHGKGAAFFPHFSQGMLGPYQQ LCIDITGCANMWGEYWDNLICTVGDLLPEVIPVHMAAVGCPISSLRTTSYTIDQAQKEPA MRFGTQVSGGDTVTRTLRLNNSSPCDIRLDWETYVPEDKEDRLVELLVFYGPPFPLRDQA GNELVCPDTPEGGCLLWSPGPSSSSEFSHETDSSVEGSSSASNRVAQKLISVILQAHEGV PSGHLYCISPKQVVVPAGGSSTIYISFTPMVLSPEILHKVECTGYALGFMSLDSKVEREI PGKRHRLQDFAVGPLKLDLHSYVRPAQLSVELDYGGSMEFQCQASDLIPEQPCSGVLSEL VTTHHLKLTNTTEIPHYFRLMVSRPFSVSQDGASQDHRAPGPGQKQECEEETASADKQLV LQAQENMLVNVSFSLSLELLSYQKLPADQTLPGVDIQQSASGEREMVFTQNLLLEYTNQT TQVVPLRAVVAVPELQLSTSWVDFGTCFVSQQRVREVYLMNLSGCRSYWTMLMGQQEPAK AAVAFRVSPNSGLLEARSANAPPTSIALQVFFTARSSELYESTMVVEGVLGEKSCTLRLR GQGSYDERYMLPHQP
Function	Essential for spermatogenesis and male fertility. May play an important role in sperm head and tail formation. May act as a tumor suppressor by inhibiting cell proliferation.
Tissue Specificity	Expressed in all tissues examined. Expression is highest in prostate and testis.

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Esophageal squamous cell carcinoma	DIS5N2GV	Definitive	Genetic Variation	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Posttranslational Modification	[2]
Prostate cancer	DISF190Y	Definitive	Altered Expression	[3]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[5]
Allergic rhinitis	DIS3U9HN	Strong	Biomarker	[6]
Arteriosclerosis	DISK5QGC	Strong	Altered Expression	[7]
Atherosclerosis	DISMN9J3	Strong	Altered Expression	[7]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[8]
Burkitt lymphoma	DIS9D5XU	Strong	Altered Expression	[9]
Cholangiocarcinoma	DIS71F6X	Strong	Posttranslational Modification	[10]
Classic Hodgkin lymphoma	DISV1LU6	Strong	Biomarker	[11]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[12]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[13]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[14]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[15]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Posttranslational Modification	[16]
Hepatocellular carcinoma	DIS0J828	Strong	Posttranslational Modification	[17]
Intrahepatic cholangiocarcinoma	DIS6GOC8	Strong	Posttranslational Modification	[5]
Lung cancer	DISCM4YA	Strong	Biomarker	[18]
Medulloblastoma	DISZD2ZL	Strong	Altered Expression	[19]
Melanoma	DIS1RRCY	Strong	Biomarker	[18]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[20]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Posttranslational Modification	[21]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[22]
Plasma cell myeloma	DIS0DFZ0	Strong	Posttranslational Modification	[23]
Renal carcinoma	DISER9XT	Strong	Biomarker	[15]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[12]
Squamous cell carcinoma	DISQVIFL	Strong	Posttranslational Modification	[24]
Stomach cancer	DISKIJSX	Strong	Biomarker	[25]
T-cell lymphoma	DISSXRTQ	Strong	Altered Expression	[11]
Adult lymphoma	DISK8IZR	moderate	Posttranslational Modification	[11]
Breast carcinoma	DIS2UE88	moderate	Altered Expression	[20]
Lymphoma	DISN6V4S	moderate	Posttranslational Modification	[11]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[26]
Pancreatic ductal carcinoma	DIS26F9Q	moderate	Biomarker	[27]
Pediatric lymphoma	DIS51BK2	moderate	Posttranslational Modification	[11]
Benign prostatic hyperplasia	DISI3CW2	Limited	Altered Expression	[3]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Genetic Variation	[28]
Colon cancer	DISVC52G	Limited	Biomarker	[29]
Colon carcinoma	DISJYKUO	Limited	Biomarker	[29]
Gastric cancer	DISXGOUK	Limited	Biomarker	[25]
Kidney cancer	DISBIPKM	Limited	Biomarker	[15]
Leiomyoma	DISLDDFN	Limited	Altered Expression	[30]
Liver cancer	DISDE4BI	Limited	Genetic Variation	[28]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[3]
Prostate neoplasm	DISHDKGQ	Limited	Altered Expression	[3]
Uterine fibroids	DISBZRMJ	Limited	Altered Expression	[30]
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⏷ Show the Full List of 48 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Deleted in lung and esophageal cancer protein 1 (DLEC1).	[31]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Deleted in lung and esophageal cancer protein 1 (DLEC1).	[32]
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References

1	Molecular cloning of a candidate tumor suppressor gene, DLC1, from chromosome 3p21.3.Cancer Res. 1999 Apr 15;59(8):1966-72.
2	Candidate tumor-suppressor gene DLEC1 is frequently downregulated by promoter hypermethylation and histone hypoacetylation in human epithelial ovarian cancer.Neoplasia. 2006 Apr;8(4):268-78. doi: 10.1593/neo.05502.
3	DLEC1, a 3p tumor suppressor, represses NF-B signaling and is methylated in prostate cancer.J Mol Med (Berl). 2015 Jun;93(6):691-701. doi: 10.1007/s00109-015-1255-5. Epub 2015 Feb 5.
4	Downregulation of DLC-1 gene by promoter methylation during primary colorectal cancer progression.Biomed Res Int. 2013;2013:181384. doi: 10.1155/2013/181384. Epub 2012 Dec 23.
5	DLEC1 methylation is associated with a better clinical outcome in patients with intrahepatic cholangiocarcinoma of the small duct subtype.Virchows Arch. 2019 Jul;475(1):49-58. doi: 10.1007/s00428-018-02511-7. Epub 2019 Jan 4.
6	Effects of desloratadine citrate disodium injection on rat models of ovalbumin-induced allergic rhinitis: involvement of T-cell responses modulation.Int Forum Allergy Rhinol. 2015 Dec;5(12):1170-6. doi: 10.1002/alr.21594. Epub 2015 Jul 8.
7	Stiffness-Induced Endothelial DLC-1 Expression Forces Leukocyte Spreading through Stabilization of the ICAM-1 Adhesome.Cell Rep. 2018 Sep 18;24(12):3115-3124. doi: 10.1016/j.celrep.2018.08.045.
8	Less frequent promoter hypermethylation of DLC-1 gene in primary breast cancers.Oncol Rep. 2004 Jul;12(1):141-4.
9	DLC-1 as a modulator of proliferation, apoptosis and migration in Burkitt's lymphoma cells.Mol Biol Rep. 2011 Mar;38(3):1915-20. doi: 10.1007/s11033-010-0311-z. Epub 2010 Oct 1.
10	Aberrant promoter CpG islands methylation of tumor suppressor genes in cholangiocarcinoma.Oncol Res. 2008;17(4):151-7. doi: 10.3727/096504008785114110.
11	Epigenetic silencing of the 3p22 tumor suppressor DLEC1 by promoter CpG methylation in non-Hodgkin and Hodgkin lymphomas.J Transl Med. 2012 Oct 11;10:209. doi: 10.1186/1479-5876-10-209.
12	Aberrant promoter methylation of DLEC1, a critical 3p22 tumor suppressor for renal cell carcinoma, is associated with more advanced tumor stage.J Urol. 2010 Aug;184(2):731-7. doi: 10.1016/j.juro.2010.03.108. Epub 2010 Jun 19.
13	IGF2-derived miR-483 mediated oncofunction by suppressing DLC-1 and associated with colorectal cancer.Oncotarget. 2016 Jul 26;7(30):48456-48466. doi: 10.18632/oncotarget.10309.
14	CDH1, DLEC1 and SFRP5 methylation panel as a prognostic marker for advanced epithelial ovarian cancer.Epigenomics. 2018 Nov;10(11):1397-1413. doi: 10.2217/epi-2018-0035. Epub 2018 Oct 16.
15	Evidence of a tumour suppressor function for DLEC1 in human breast cancer.Anticancer Res. 2010 Apr;30(4):1079-82.
16	DLEC1 is not silenced solely by promoter methylation in head and neck squamous cell carcinoma.Gene. 2015 May 25;563(1):83-6. doi: 10.1016/j.gene.2015.03.004. Epub 2015 Mar 6.
17	Epigenetic mechanisms regulating the development of hepatocellular carcinoma and their promise for therapeutics.Hepatol Int. 2017 Jan;11(1):45-53. doi: 10.1007/s12072-016-9743-4. Epub 2016 Jun 7.
18	MIRA-assisted microarray analysis, a new technology for the determination of DNA methylation patterns, identifies frequent methylation of homeodomain-containing genes in lung cancer cells.Cancer Res. 2006 Aug 15;66(16):7939-47. doi: 10.1158/0008-5472.CAN-06-1888.
19	Epigenetic inactivation of DLC-1 in supratentorial primitive neuroectodermal tumor.Hum Pathol. 2005 Jan;36(1):36-43. doi: 10.1016/j.humpath.2004.09.021.
20	DLC-1 expression levels in breast cancer assessed by qRT- PCR are negatively associated with malignancy.Asian Pac J Cancer Prev. 2012;13(4):1231-3. doi: 10.7314/apjcp.2012.13.4.1231.
21	Epigenetic silencing of the tumor suppressor genes SPI1, PRDX2, KLF4, DLEC1, and DAPK1 in childhood and adolescent lymphomas.Pediatr Hematol Oncol. 2018 Mar;35(2):131-144. doi: 10.1080/08880018.2018.1467986. Epub 2018 Jul 18.
22	Expression level and methylation status of three tumor suppressor genes, DLEC1, ITGA9 and MLH1, in non-small cell lung cancer.Med Oncol. 2016 Jul;33(7):75. doi: 10.1007/s12032-016-0791-3. Epub 2016 Jun 10.
23	High-frequency promoter hypermethylation of the deleted in liver cancer-1 gene in multiple myeloma.J Clin Pathol. 2006 Sep;59(9):947-51. doi: 10.1136/jcp.2005.031377. Epub 2006 Feb 17.
24	A low DNA methylation epigenotype in lung squamous cell carcinoma and its association with idiopathic pulmonary fibrosis and poorer prognosis.Int J Cancer. 2020 Jan 15;146(2):388-399. doi: 10.1002/ijc.32532. Epub 2019 Jul 8.
25	The diagnosis value of promoter methylation of UCHL1 in the serum for progression of gastric cancer.Biomed Res Int. 2015;2015:741030. doi: 10.1155/2015/741030. Epub 2015 Oct 15.
26	Upregulation of DLC-1 inhibits pancreatic cancer progression: Studies with clinical samples and a pancreatic cancer model.Oncol Lett. 2019 Nov;18(5):5600-5606. doi: 10.3892/ol.2019.10871. Epub 2019 Sep 16.
27	DLC-1 is a candidate biomarker methylated and down-regulated in pancreatic ductal adenocarcinoma.Tumour Biol. 2013 Oct;34(5):2857-61. doi: 10.1007/s13277-013-0846-4. Epub 2013 May 17.
28	Hepatitis B core protein promotes liver cancer metastasis through miR-382-5p/DLC-1 axis.Biochim Biophys Acta Mol Cell Res. 2018 Jan;1865(1):1-11. doi: 10.1016/j.bbamcr.2017.09.020. Epub 2017 Oct 3.
29	Tumor suppressor DLC-1 induces apoptosis and inhibits the growth and invasion of colon cancer cells through the Wnt/-catenin signaling pathway.Oncol Rep. 2014 May;31(5):2270-8. doi: 10.3892/or.2014.3057. Epub 2014 Mar 5.
30	Different methylation levels in the KLF4, ATF3 and DLEC1 genes in the myometrium and in corpus uteri mesenchymal tumours as assessed by MS-HRM.Pathol Res Pract. 2019 Aug;215(8):152465. doi: 10.1016/j.prp.2019.152465. Epub 2019 May 23.
31	The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
32	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.