Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2C6TH2)

• DOT Name: Transcription factor IIIB 50 kDa subunit (BRF2)
• Synonyms: TFIIIB50; hTFIIIB50; B-related factor 2; BRF-2; hBRFU
• Gene Name: BRF2
• Related Disease:
  Breast cancer
  Esophageal squamous cell carcinoma
  Lung cancer
  Lung carcinoma
  Lung squamous cell carcinoma
  Squamous cell carcinoma
  Advanced cancer
  Breast carcinoma
  Non-small-cell lung cancer
  Neoplasm
• UniProt ID: BRF2_HUMAN
• PDB ID: 4ROC; 4ROD; 4ROE; 5N9G; 8ITY; 8IUE; 8IUH
• Pfam ID: PF08271
• Sequence:
  MPGRGRCPDCGSTELVEDSHYSQSQLVCSDCGCVVTEGVLTTTFSDEGNLREVTYSRSTG
  ENEQVSRSQQRGLRRVRDLCRVLQLPPTFEDTAVAYYQQAYRHSGIRAARLQKKEVLVGC
  CVLITCRQHNWPLTMGAICTLLYADLDVFSSTYMQIVKLLGLDVPSLCLAELVKTYCSSF
  KLFQASPSVPAKYVEDKEKMLSRTMQLVELANETWLVTGRHPLPVITAATFLAWQSLQPA
  DRLSCSLARFCKLANVDLPYPASSRLQELLAVLLRMAEQLAWLRVLRLDKRSVVKHIGDL
  LQHRQSLVRSAFRDGTAEVETREKEPPGWGQGQGEGEVGNNSLGLPQGKRPASPALLLPP
  CMLKSPKRICPVPPVSTVTGDENISDSEIEQYLRTPQEVRDFQRAQAARQAATSVPNPP
• Function: General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites. Contributes to the regulation of gene expression; functions as activator in the absence of oxidative stress. Down-regulates expression of target genes in response to oxidative stress. Overexpression protects cells against apoptosis in response to oxidative stress.
• Reactome Pathway:
  RNA Polymerase III Transcription Initiation From Type 3 Promoter (R-HSA-76071)
  RNA Polymerase III Abortive And Retractive Initiation (R-HSA-749476)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Breast cancer	DIS7DPX1	Strong	Biomarker	[1]
Esophageal squamous cell carcinoma	DIS5N2GV	Strong	Biomarker	[2]
Lung cancer	DISCM4YA	Strong	Biomarker	[3]
Lung carcinoma	DISTR26C	Strong	Biomarker	[3]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[4]
Squamous cell carcinoma	DISQVIFL	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[5]
Breast carcinoma	DIS2UE88	moderate	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	moderate	Altered Expression	[6]
Neoplasm	DISZKGEW	Limited	Altered Expression	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[10]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[9]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[13]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[14]
Selenium	DM25CGV	Approved	Selenium increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[15]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[16]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[17]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[9]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Transcription factor IIIB 50 kDa subunit (BRF2).	[18]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Transcription factor IIIB 50 kDa subunit (BRF2).	[11]

References

• [1] Understanding the functional impact of copy number alterations in breast cancer using a network modeling approach.Mol Biosyst. 2016 Mar;12(3):963-72. doi: 10.1039/c5mb00655d.
• [2] BRF2 as a promising indicator for radical lymph-node dissection surgery in patients with cN0 squamous cell carcinoma of the middle thoracic esophagus.Surg Today. 2019 Feb;49(2):158-169. doi: 10.1007/s00595-018-1711-2. Epub 2018 Sep 4.
• [3] Long noncoding RNA MNX1-AS1 contributes to lung cancer progression through the miR-527/BRF2 pathway.J Cell Physiol. 2019 Aug;234(8):13843-13850. doi: 10.1002/jcp.28064. Epub 2019 Jan 7.
• [4] Integrative genomic analyses identify BRF2 as a novel lineage-specific oncogene in lung squamous cell carcinoma.PLoS Med. 2010 Jul 27;7(7):e1000315. doi: 10.1371/journal.pmed.1000315.
• [5] Induction of proto-oncogene BRF2 in breast cancer cells by the dietary soybean isoflavone daidzein.BMC Cancer. 2015 Nov 16;15:905. doi: 10.1186/s12885-015-1914-5.
• [6] MicroRNA-373 Inhibits Cell Proliferation and Invasion via Targeting BRF2 in Human Non-small Cell Lung Cancer A549 Cell Line.Cancer Res Treat. 2018 Jul;50(3):936-949. doi: 10.4143/crt.2017.302. Epub 2017 Oct 12.
• [7] TFIIB-related factor 2 is associated with poor prognosis of nonsmall cell lung cancer patients through promoting tumor epithelial-mesenchymal transition.Biomed Res Int. 2014;2014:530786. doi: 10.1155/2014/530786. Epub 2014 Mar 17.
• [8] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [12] 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.
• [13] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [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] 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.
• [16] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [17] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [18] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.