Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV5A6LL)

DOT Name	Breast cancer metastasis-suppressor 1 (BRMS1)
Gene Name	BRMS1
Related Disease	Adenocarcinoma ( ) Squamous cell carcinoma ( ) Thyroid gland papillary carcinoma ( ) Thyroid gland undifferentiated (anaplastic) carcinoma ( ) Bladder cancer ( ) Cervical cancer ( ) Cervical carcinoma ( ) Colorectal carcinoma ( ) Epithelial ovarian cancer ( ) Fanconi anemia complementation group A ( ) Fanconi's anemia ( ) Glioma ( ) Hepatocellular carcinoma ( ) Human papillomavirus infection ( ) Lung cancer ( ) Lung carcinoma ( ) Melanoma ( ) Metastatic malignant neoplasm ( ) Nasopharyngeal carcinoma ( ) Non-small-cell lung cancer ( ) Ovarian cancer ( ) Ovarian neoplasm ( ) Prostate cancer ( ) Prostate carcinoma ( ) Rectal carcinoma ( ) Triple negative breast cancer ( ) Urinary bladder cancer ( ) Urinary bladder neoplasm ( ) Breast neoplasm ( ) Choriocarcinoma ( ) Lung adenocarcinoma ( ) Bone osteosarcoma ( ) Breast disorder ( ) Cutaneous melanoma ( ) Ductal breast carcinoma in situ ( ) Gastric cancer ( ) Invasive breast carcinoma ( ) Lung neoplasm ( ) Metastatic sarcoma ( ) Osteosarcoma ( ) Stomach cancer ( )
UniProt ID	BRMS1_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2XUS; 4AUV
Pfam ID	PF08598
Sequence	MPVQPPSKDTEEMEAEGDSAAEMNGEEEESEEERSGSQTESEEESSEMDDEDYERRRSEC VSEMLDLEKQFSELKEKLFRERLSQLRLRLEEVGAERAPEYTEPLGGLQRSLKIRIQVAG IYKGFCLDVIRNKYECELQGAKQHLESEKLLLYDTLQGELQERIQRLEEDRQSLDLSSEW WDDKLHARGSSRSWDSLPPSKRKKAPLVSGPYIVYMLQEIDILEDWTAIKKARAAVSPQK RKSDGP
Function	Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis. May be a mediator of metastasis suppression in breast carcinoma.
Tissue Specificity	Expression levels are higher in term placentas than in early placentas. Low levels of expression observed in normal pregnancies and in molar pregnancies.
Reactome Pathway	Potential therapeutics for SARS (R-HSA-9679191 ) HDACs deacetylate histones (R-HSA-3214815 )

Molecular Interaction Atlas (MIA) of This DOT

41 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adenocarcinoma	DIS3IHTY	Definitive	Posttranslational Modification	[1]
Squamous cell carcinoma	DISQVIFL	Definitive	Posttranslational Modification	[1]
Thyroid gland papillary carcinoma	DIS48YMM	Definitive	Altered Expression	[2]
Thyroid gland undifferentiated (anaplastic) carcinoma	DISYBB1W	Definitive	Altered Expression	[2]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[3]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[4]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[4]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[6]
Fanconi anemia complementation group A	DIS8PZLI	Strong	Biomarker	[7]
Fanconi's anemia	DISGW6Q8	Strong	Biomarker	[7]
Glioma	DIS5RPEH	Strong	Biomarker	[8]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[9]
Human papillomavirus infection	DISX61LX	Strong	Posttranslational Modification	[4]
Lung cancer	DISCM4YA	Strong	Biomarker	[10]
Lung carcinoma	DISTR26C	Strong	Biomarker	[10]
Melanoma	DIS1RRCY	Strong	Biomarker	[11]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[12]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[13]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[14]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Altered Expression	[15]
Prostate carcinoma	DISMJPLE	Strong	Altered Expression	[15]
Rectal carcinoma	DIS8FRR7	Strong	Altered Expression	[5]
Triple negative breast cancer	DISAMG6N	Strong	Altered Expression	[16]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[3]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[3]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[17]
Choriocarcinoma	DISDBVNL	moderate	Altered Expression	[18]
Lung adenocarcinoma	DISD51WR	moderate	Altered Expression	[19]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[20]
Breast disorder	DISJTGMA	Limited	Altered Expression	[21]
Cutaneous melanoma	DIS3MMH9	Limited	Biomarker	[22]
Ductal breast carcinoma in situ	DISLCJY7	Limited	Altered Expression	[21]
Gastric cancer	DISXGOUK	Limited	Biomarker	[23]
Invasive breast carcinoma	DISANYTW	Limited	Altered Expression	[24]
Lung neoplasm	DISVARNB	Limited	Biomarker	[14]
Metastatic sarcoma	DISKYC7V	Limited	Biomarker	[21]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[20]
Stomach cancer	DISKIJSX	Limited	Biomarker	[23]
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⏷ Show the Full List of 41 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[25]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[26]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[27]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[28]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[29]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[30]
Selenium	DM25CGV	Approved	Selenium increases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[31]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[32]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[31]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[36]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[37]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Breast cancer metastasis-suppressor 1 (BRMS1).	[38]
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⏷ Show the Full List of 12 Drug(s)

3 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 affects the methylation of Breast cancer metastasis-suppressor 1 (BRMS1).	[33]
TAK-243	DM4GKV2	Phase 1	TAK-243 increases the sumoylation of Breast cancer metastasis-suppressor 1 (BRMS1).	[34]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Breast cancer metastasis-suppressor 1 (BRMS1).	[35]
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References

1	BRMS1 transcriptional repression correlates with CpG island methylation and advanced pathological stage in non-small cell lung cancer.J Pathol. 2010 Jun;221(2):229-37. doi: 10.1002/path.2707.
2	BRMS1 downregulation is a poor prognostic biomarker in anaplastic thyroid carcinoma patients.Onco Targets Ther. 2019 Aug 28;12:6937-6945. doi: 10.2147/OTT.S219506. eCollection 2019.
3	The relationship of BRMS1 and RhoGDI2 gene expression to metastatic potential in lineage related human bladder cancer cell lines.Clin Exp Metastasis. 2000;18(6):519-25. doi: 10.1023/a:1011819621859.
4	Gene promoter methylation and protein expression of BRMS1 in uterine cervix in relation to high-risk human papilloma virus infection and cancer.Tumour Biol. 2017 Apr;39(4):1010428317697557. doi: 10.1177/1010428317697557.
5	Effect of BRMS1 on tumorigenicity and metastasis of human rectal cancer.Cell Biochem Biophys. 2014 Sep;70(1):505-9. doi: 10.1007/s12013-014-9948-x.
6	Narrowing the field: cancer-specific promoters for mitochondrially-targeted p53-BH3 fusion gene therapy in ovarian cancer.J Ovarian Res. 2019 Apr 30;12(1):38. doi: 10.1186/s13048-019-0514-4.
7	BRMS1 participates in regulating cell sensitivity to DNA interstrand crosslink damage by interacting with FANCI.Oncol Rep. 2019 Jan;41(1):552-558. doi: 10.3892/or.2018.6816. Epub 2018 Oct 24.
8	BRMS1 suppresses glioma progression by regulating invasion, migration and adhesion of glioma cells.PLoS One. 2014 May 30;9(5):e98544. doi: 10.1371/journal.pone.0098544. eCollection 2014.
9	miR-346 Promotes HCC Progression by Suppressing Breast Cancer Metastasis Suppressor 1 Expression.Oncol Res. 2018 Aug 23;26(7):1073-1081. doi: 10.3727/096504017X15145088802439. Epub 2018 Jan 2.
10	BRMS1 suppresses lung cancer metastases through an E3 ligase function on histone acetyltransferase p300.Cancer Res. 2013 Feb 15;73(4):1308-17. doi: 10.1158/0008-5472.CAN-12-2489. Epub 2012 Dec 26.
11	Expression of breast cancer metastasis suppressor-1, BRMS-1, in human breast cancer and the biological impact of BRMS-1 on the migration of breast cancer cells.Anticancer Res. 2014 Mar;34(3):1417-26.
12	Significance of BRCA1 expression in breast and ovarian cancer patients with brain metastasis - A multicentre study.Adv Med Sci. 2019 Sep;64(2):235-240. doi: 10.1016/j.advms.2018.12.007. Epub 2019 Feb 26.
13	miR-346 promotes migration and invasion of nasopharyngeal carcinoma cells via targeting BRMS1.J Biochem Mol Toxicol. 2016 Dec;30(12):602-607. doi: 10.1002/jbt.21827. Epub 2016 Aug 8.
14	Loss of BRMS1 promotes a mesenchymal phenotype through NF-B-dependent regulation of Twist1.Mol Cell Biol. 2015 Jan;35(1):303-17. doi: 10.1128/MCB.00869-14. Epub 2014 Nov 3.
15	Breast cancer metastasis suppressor 1 (BRMS1) suppresses prostate cancer progression by inducing apoptosis and regulating invasion.Eur Rev Med Pharmacol Sci. 2017 Jan;21(1):68-75.
16	Down-regulation of BRMS1 by DNA hypermethylation and its association with metastatic progression in triple-negative breast cancer.Int J Clin Exp Pathol. 2015 Sep 1;8(9):11076-83. eCollection 2015.
17	Development and validation of a multiplex methylation specific PCR-coupled liquid bead array for liquid biopsy analysis.Clin Chim Acta. 2016 Oct 1;461:156-64. doi: 10.1016/j.cca.2016.08.003. Epub 2016 Aug 7.
18	Transcriptional expression of genes involved in cell invasion and migration by normal and tumoral trophoblast cells.J Clin Endocrinol Metab. 2002 Nov;87(11):5336-9. doi: 10.1210/jc.2002-021093.
19	BRMS1 Expression in Surgically Resected Lung Adenocarcinoma Predicts Future Metastases and IsAssociated with a Poor Prognosis.J Thorac Oncol. 2018 Jan;13(1):73-84. doi: 10.1016/j.jtho.2017.10.006. Epub 2017 Oct 31.
20	MicroRNA-3200-5p Promotes Osteosarcoma Cell Invasion via Suppression of BRMS1.Mol Cells. 2018 Jun;41(6):523-531. doi: 10.14348/molcells.2018.2200. Epub 2018 Jun 11.
21	Multiple forms of BRMS1 are differentially expressed in the MCF10 isogenic breast cancer progression model.Clin Exp Metastasis. 2009;26(2):89-96. doi: 10.1007/s10585-008-9216-9. Epub 2008 Oct 8.
22	Suppression of human melanoma metastasis by the metastasis suppressor gene, BRMS1.Exp Cell Res. 2002 Feb 15;273(2):229-39. doi: 10.1006/excr.2001.5452.
23	Epigenetics mechanisms mediate the miR-125a/BRMS1 axis to regulate invasion and metastasis in gastric cancer.Onco Targets Ther. 2019 Sep 12;12:7513-7525. doi: 10.2147/OTT.S210376. eCollection 2019.
24	Reduced expression of the breast cancer metastasis suppressor 1 mRNA is correlated with poor progress in breast cancer.Clin Cancer Res. 2006 Nov 1;12(21):6410-4. doi: 10.1158/1078-0432.CCR-06-1347.
25	Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
26	Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
27	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.
28	Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
29	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.
30	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.
31	Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
32	Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
33	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.
34	Inhibiting ubiquitination causes an accumulation of SUMOylated newly synthesized nuclear proteins at PML bodies. J Biol Chem. 2019 Oct 18;294(42):15218-15234. doi: 10.1074/jbc.RA119.009147. Epub 2019 Jul 8.
35	Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
36	A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
37	Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
38	Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.