Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT79EXZ7)

• DOT Name: Migration and invasion-inhibitory protein (MIIP)
• Synonyms: IGFBP2-binding protein; Invasion-inhibitory protein 45; IIp45
• Gene Name: MIIP
• Related Disease:
  Adult glioblastoma
  Breast cancer
  Breast carcinoma
  Colorectal carcinoma
  Glioblastoma multiforme
  Glioma
  Lung adenocarcinoma
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Metastatic malignant neoplasm
  Pancreatic cancer
  Gastric cancer
  Nasopharyngeal carcinoma
  Stomach cancer
• UniProt ID: MIIP_HUMAN
• Pfam ID: PF15734
• Sequence:
  MVEAEELAQLRLLNLELLRQLWVGQDAVRRSVARAASESSLESSSSYNSETPSTPETSST
  SLSTSCPRGRSSVWGPPDACRGDLRDVARSGVASLPPAKCQHQESLGRPRPHSAPSLGTS
  SLRDPEPSGRLGDPGPQEAQTPRSILAQQSKLSKPRVTFSEESAVPKRSWRLRPYLGYDW
  IAGSLDTSSSITSQPEAFFSKLQEFRETNKEECICSHPEPQLPGLRESSGSGVEEDHECV
  YCYRVNRRLFPVPVDPGTPCRLCRTPRDQQGPGTLAQPAHVRVSIPLSILEPPHRYHIHR
  RKSFDASDTLALPRHCLLGWDIFPPKSEKSSAPRNLDLWSSVSAEAQHQKLSGTSSPFHP
  ASPMQMLPPTPTWSVPQVPRPHVPRQKP
• Function: Inhibits glioma cells invasion and down-regulates adhesion- and motility-associated genes such as NFKB2 and ICAM1. Exhibits opposing effects to IGFBP2 on cell invasion.
• Tissue Specificity: Ubiquitous. Isoform 1 is expressed in brain but underexpressed in glioma tissues, at protein level. Isoform 2 is not detected in normal organs, but is expressed in gliomas with increasing levels with glioma progression. On the contrary, at protein level, isoform 2 is not detected in gliomas, suggesting that this isoform is unstable in glioma cells.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[2]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[1]
Glioma	DIS5RPEH	Strong	Biomarker	[3]
Lung adenocarcinoma	DISD51WR	Strong	Altered Expression	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[4]
Prostate cancer	DISF190Y	Strong	Biomarker	[6]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[6]
Metastatic malignant neoplasm	DIS86UK6	moderate	Biomarker	[7]
Pancreatic cancer	DISJC981	moderate	Altered Expression	[8]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[9]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[10]
Stomach cancer	DISKIJSX	Limited	Altered Expression	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Migration and invasion-inhibitory protein (MIIP).	[11]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Migration and invasion-inhibitory protein (MIIP).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Migration and invasion-inhibitory protein (MIIP).	[12]
Selenium	DM25CGV	Approved	Selenium increases the expression of Migration and invasion-inhibitory protein (MIIP).	[13]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Migration and invasion-inhibitory protein (MIIP).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Migration and invasion-inhibitory protein (MIIP).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Migration and invasion-inhibitory protein (MIIP).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Migration and invasion-inhibitory protein (MIIP).	[18]

References

• [1] Inhibition of gliomagenesis and attenuation of mitotic transition by MIIP.Oncogene. 2010 Jun 17;29(24):3501-8. doi: 10.1038/onc.2010.114. Epub 2010 Apr 26.
• [2] Upregulation of MIIP regulates human breast cancer proliferation, invasion and migration by mediated by IGFBP2.Pathol Res Pract. 2019 Jul;215(7):152440. doi: 10.1016/j.prp.2019.152440. Epub 2019 May 6.
• [3] MIIP haploinsufficiency induces chromosomal instability and promotes tumour progression in colorectal cancer.J Pathol. 2017 Jan;241(1):67-79. doi: 10.1002/path.4823. Epub 2016 Nov 24.
• [4] MIIP accelerates epidermal growth factor receptor protein turnover and attenuates proliferation in non-small cell lung cancer.Oncotarget. 2016 Feb 23;7(8):9118-34. doi: 10.18632/oncotarget.7001.
• [5] MIIP inhibits the growth of prostate cancer via interaction with PP1 and negative modulation of AKT signaling.Cell Commun Signal. 2019 May 15;17(1):44. doi: 10.1186/s12964-019-0355-1.
• [6] Correction to: MIIP inhibits the growth of prostate cancer via interaction with PP1 and negative modulation of AKT signaling.Cell Commun Signal. 2019 Oct 21;17(1):130. doi: 10.1186/s12964-019-0441-4.
• [7] PKC phosphorylates MIIP and promotes colorectal cancer metastasis through inhibition of RelA deacetylation.Nat Commun. 2017 Oct 16;8(1):939. doi: 10.1038/s41467-017-01024-2.
• [8] MiRNA-646-mediated reciprocal repression between HIF-1 and MIIP contributes to tumorigenesis of pancreatic cancer.Oncogene. 2018 Mar;37(13):1743-1758. doi: 10.1038/s41388-017-0082-2. Epub 2018 Jan 18.
• [9] MIIP is downregulated in gastric cancer and its forced expression inhibits proliferation and invasion of gastric cancer cells in vitro and in vivo.Onco Targets Ther. 2018 Dec 11;11:8951-8964. doi: 10.2147/OTT.S173393. eCollection 2018.
• [10] MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells.Oncol Lett. 2018 Jun;15(6):9471-9479. doi: 10.3892/ol.2018.8524. Epub 2018 Apr 18.
• [11] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] 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.
• [14] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [15] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [16] 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.
• [17] 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.
• [18] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.