Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1T5KM6)

• DOT Name: B-cell CLL/lymphoma 6 member B protein (BCL6B)
• Synonyms: Bcl6-associated zinc finger protein; Zinc finger protein 62
• Gene Name: BCL6B
• Related Disease:
  Metastatic malignant neoplasm
  Colorectal carcinoma
  Hepatocellular carcinoma
  Influenza
  Liver cirrhosis
  Neoplasm
  Gastric cancer
  Stomach cancer
  Advanced cancer
• UniProt ID: BCL6B_HUMAN
• Pfam ID: PF00651 ; PF00096
• Sequence:
  MGSPAAPEGALGYVREFTRHSSDVLGNLNELRLRGILTDVTLLVGGQPLRAHKAVLIACS
  GFFYSIFRGRAGVGVDVLSLPGGPEARGFAPLLDFMYTSRLRLSPATAPAVLAAATYLQM
  EHVVQACHRFIQASYEPLGISLRPLEAEPPTPPTAPPPGSPRRSEGHPDPPTESRSCSQG
  PPSPASPDPKACNWKKYKYIVLNSQASQAGSLVGERSSGQPCPQARLPSGDEASSSSSSS
  SSSSEEGPIPGPQSRLSPTAATVQFKCGAPASTPYLLTSQAQDTSGSPSERARPLPGSEF
  FSCQNCEAVAGCSSGLDSLVPGDEDKPYKCQLCRSSFRYKGNLASHRTVHTGEKPYHCSI
  CGARFNRPANLKTHSRIHSGEKPYKCETCGSRFVQVAHLRAHVLIHTGEKPYPCPTCGTR
  FRHLQTLKSHVRIHTGEKPYHCDPCGLHFRHKSQLRLHLRQKHGAATNTKVHYHILGGP
• Function: Acts as a sequence-specific transcriptional repressor in association with BCL6. May function in a narrow stage or be related to some events in the early B-cell development.
• Tissue Specificity: Ubiquitously expressed with higher expression found in heart and placenta.

Molecular Interaction Atlas (MIA) of This DOT

9 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metastatic malignant neoplasm	DIS86UK6	Definitive	Biomarker	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Influenza	DIS3PNU3	Strong	Biomarker	[4]
Liver cirrhosis	DIS4G1GX	Strong	Altered Expression	[1]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Gastric cancer	DISXGOUK	moderate	Altered Expression	[6]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[6]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of B-cell CLL/lymphoma 6 member B protein (BCL6B).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of B-cell CLL/lymphoma 6 member B protein (BCL6B).	[9]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of B-cell CLL/lymphoma 6 member B protein (BCL6B).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of B-cell CLL/lymphoma 6 member B protein (BCL6B).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of B-cell CLL/lymphoma 6 member B protein (BCL6B).	[8]

References

• [1] BCL6B expression in hepatocellular carcinoma and its efficacy in the inhibition of liver damage and fibrogenesis.Oncotarget. 2015 Aug 21;6(24):20252-65. doi: 10.18632/oncotarget.3857.
• [2] BCL6B suppresses proliferation and migration of colorectal carcinoma cells through inhibition of the PI3K/AKT signaling pathway.Int J Mol Med. 2018 May;41(5):2660-2668. doi: 10.3892/ijmm.2018.3451. Epub 2018 Feb 1.
• [3] Epigenetic silencing of BCL6B inactivates p53 signaling and causes human hepatocellular carcinoma cell resist to 5-FU.Oncotarget. 2015 May 10;6(13):11547-60. doi: 10.18632/oncotarget.3413.
• [4] BCL6b mediates the enhanced magnitude of the secondary response of memory CD8+ T lymphocytes.Proc Natl Acad Sci U S A. 2005 May 24;102(21):7418-25. doi: 10.1073/pnas.0501585102. Epub 2005 Apr 15.
• [5] Tumor suppressive BTB/POZ zinc-finger protein ZBTB28 inhibits oncogenic BCL6/ZBTB27 signaling to maintain p53 transcription in multiple carcinogenesis.Theranostics. 2019 Oct 18;9(26):8182-8195. doi: 10.7150/thno.34983. eCollection 2019.
• [6] Inhibition of Bcl6b promotes gastric cancer by amplifying inflammation in mice.Cell Commun Signal. 2019 Jul 9;17(1):72. doi: 10.1186/s12964-019-0387-6.
• [7] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [9] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [10] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [11] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.