Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJIW47U)

• DOT Name: Breast cancer metastasis-suppressor 1-like protein (BRMS1L)
• Synonyms: BRMS1-homolog protein p40; BRMS1-like protein p40
• Gene Name: BRMS1L
• Related Disease:
  Gastric cancer
  Stomach cancer
  Adult glioblastoma
  Brain cancer
  Brain neoplasm
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Epithelial ovarian cancer
  Glioblastoma multiforme
  Glioma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Malignant glioma
  Metastatic malignant neoplasm
  Non-small-cell lung cancer
  Ovarian cancer
  Ovarian neoplasm
  Prostate cancer
  Prostate carcinoma
  Advanced cancer
  Neoplasm
  Bone osteosarcoma
  Melanoma
  Osteosarcoma
• UniProt ID: BRM1L_HUMAN
• Pfam ID: PF08598
• Sequence:
  MPVHSRGDKKETNHHDEMEVDYAENEGSSSEDEDTESSSVSEDGDSSEMDDEDCERRRME
  CLDEMSNLEKQFTDLKDQLYKERLSQVDAKLQEVIAGKAPEYLEPLATLQENMQIRTKVA
  GIYRELCLESVKNKYECEIQASRQHCESEKLLLYDTVQSELEEKIRRLEEDRHSIDITSE
  LWNDELQSRKKRKDPFSPDKKKPVVVSGPYIVYMLQDLDILEDWTTIRKAMATLGPHRVK
  TEPPVKLEKHLHSARSEEGRLYYDGEWYIRGQTICIDKKDECPTSAVITTINHDEVWFKR
  PDGSKSKLYISQLQKGKYSIKHS
• Function: Involved in the histone deacetylase (HDAC1)-dependent transcriptional repression activity. When overexpressed in lung cancer cell line that lacks p53/TP53 expression, inhibits cell growth.

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gastric cancer	DISXGOUK	Definitive	Altered Expression	[1]
Stomach cancer	DISKIJSX	Definitive	Altered Expression	[1]
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[2]
Brain cancer	DISBKFB7	Strong	Altered Expression	[3]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[3]
Breast cancer	DIS7DPX1	Strong	Biomarker	[4]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Breast neoplasm	DISNGJLM	Strong	Posttranslational Modification	[5]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[6]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[2]
Glioma	DIS5RPEH	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[7]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[8]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[2]
Metastatic malignant neoplasm	DIS86UK6	Strong	Biomarker	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[10]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[6]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[6]
Prostate cancer	DISF190Y	Strong	Biomarker	[11]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[11]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[12]
Neoplasm	DISZKGEW	moderate	Altered Expression	[1]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[13]
Melanoma	DIS1RRCY	Limited	Biomarker	[14]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[13]

10 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-like protein (BRMS1L).	[15]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[16]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[17]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[18]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[19]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[20]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[21]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[22]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[19]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[24]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
TAK-243	DM4GKV2	Phase 1	TAK-243 decreases the sumoylation of Breast cancer metastasis-suppressor 1-like protein (BRMS1L).	[23]

References

• [1] 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.
• [2] Decreased BRMS1L expression is correlated with glioma grade and predicts poor survival in glioblastoma via an invasive phenotype.Cancer Biomark. 2018;22(2):311-316. doi: 10.3233/CBM-171019.
• [3] Identification and characterization of a metastatic suppressor BRMS1L as a target gene of p53.Cancer Sci. 2017 Dec;108(12):2413-2421. doi: 10.1111/cas.13420. Epub 2017 Nov 6.
• [4] 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.
• [5] Breast cancer metastasis suppressor-1 promoter methylation in primary breast tumors and corresponding circulating tumor cells.Mol Cancer Res. 2013 Oct;11(10):1248-57. doi: 10.1158/1541-7786.MCR-13-0096. Epub 2013 Jun 6.
• [6] Oncogene miR-934 promotes ovarian cancer cell proliferation and inhibits cell apoptosis through targeting BRMS1L.Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5595-5602. doi: 10.26355/eurrev_201907_18293.
• [7] MicroRNA-423 enhances the invasiveness of hepatocellular carcinoma via regulation of BRMS1.Am J Transl Res. 2017 Dec 15;9(12):5576-5584. eCollection 2017.
• [8] 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.
• [9] BRMS1L suppresses ovarian cancer metastasis via inhibition of the -catenin-wnt pathway.Exp Cell Res. 2018 Oct 1;371(1):214-221. doi: 10.1016/j.yexcr.2018.08.013. Epub 2018 Aug 15.
• [10] 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.
• [11] 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.
• [12] Fascin expression is inversely correlated with breast cancer metastasis suppressor 1 and predicts a worse survival outcome in node-negative breast cancer patients.J Cancer. 2017 Sep 6;8(16):3122-3129. doi: 10.7150/jca.22046. eCollection 2017.
• [13] 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.
• [14] 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.
• [15] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [16] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [17] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [18] 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.
• [19] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [20] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [21] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [22] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [23] 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.
• [24] Neurotoxicity and underlying cellular changes of 21 mitochondrial respiratory chain inhibitors. Arch Toxicol. 2021 Feb;95(2):591-615. doi: 10.1007/s00204-020-02970-5. Epub 2021 Jan 29.