Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXDF9T3)

• DOT Name: Coronin-1C (CORO1C)
• Synonyms: Coronin-3; hCRNN4
• Gene Name: CORO1C
• Related Disease:
  Advanced cancer
  Brain neoplasm
  Hepatocellular carcinoma
  IgA nephropathy
  Lung squamous cell carcinoma
  Metastatic malignant neoplasm
  Neoplasm
  Non-small-cell lung cancer
  Prostate cancer
  Prostate carcinoma
  Triple negative breast cancer
  Coronary heart disease
  Spinal muscular atrophy
  AIDS-related lymphoma
  Bone osteosarcoma
  Breast cancer
  Breast carcinoma
  Gastric cancer
  Kidney cancer
  Lung cancer
  Lung carcinoma
  Osteosarcoma
  Renal cell carcinoma
  Stomach cancer
• UniProt ID: COR1C_HUMAN
• PDB ID: 7STY
• Pfam ID: PF08953 ; PF00400 ; PF16300
• Sequence:
  MRRVVRQSKFRHVFGQAVKNDQCYDDIRVSRVTWDSSFCAVNPRFVAIIIEASGGGAFLV
  LPLHKTGRIDKSYPTVCGHTGPVLDIDWCPHNDQVIASGSEDCTVMVWQIPENGLTLSLT
  EPVVILEGHSKRVGIVAWHPTARNVLLSAGCDNAIIIWNVGTGEALINLDDMHSDMIYNV
  SWNRNGSLICTASKDKKVRVIDPRKQEIVAEKEKAHEGARPMRAIFLADGNVFTTGFSRM
  SERQLALWNPKNMQEPIALHEMDTSNGVLLPFYDPDTSIIYLCGKGDSSIRYFEITDESP
  YVHYLNTFSSKEPQRGMGYMPKRGLDVNKCEIARFFKLHERKCEPIIMTVPRKSDLFQDD
  LYPDTAGPEAALEAEEWFEGKNADPILISLKHGYIPGKNRDLKVVKKNILDSKPTANKKC
  DLISIPKKTTDTASVQNEAKLDEILKEIKSIKDTICNQDERISKLEQQMAKIAA
• Function: Plays a role in directed cell migration by regulating the activation and subcellular location of RAC1. Increases the presence of activated RAC1 at the leading edge of migrating cells. Required for normal organization of the cytoskeleton, including the actin cytoskeleton, microtubules and the vimentin intermediate filaments. Plays a role in endoplasmic reticulum-associated endosome fission: localizes to endosome membrane tubules and promotes recruitment of TMCC1, leading to recruitment of the endoplasmic reticulum to endosome tubules for fission. Endosome membrane fission of early and late endosomes is essential to separate regions destined for lysosomal degradation from carriers to be recycled to the plasma membrane. Required for normal cell proliferation, cell migration, and normal formation of lamellipodia. Required for normal distribution of mitochondria within cells; [Isoform 3]: Involved in myogenic differentiation.
• Tissue Specificity: Ubiquitous.

Molecular Interaction Atlas (MIA) of This DOT

24 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Brain neoplasm	DISY3EKS	Strong	Altered Expression	[2]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[3]
IgA nephropathy	DISZ8MTK	Strong	Biomarker	[4]
Lung squamous cell carcinoma	DISXPIBD	Strong	Biomarker	[5]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[6]
Neoplasm	DISZKGEW	Strong	Biomarker	[1]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[7]
Prostate cancer	DISF190Y	Strong	Biomarker	[8]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[8]
Triple negative breast cancer	DISAMG6N	Strong	Biomarker	[9]
Coronary heart disease	DIS5OIP1	moderate	Genetic Variation	[10]
Spinal muscular atrophy	DISTLKOB	moderate	Biomarker	[11]
AIDS-related lymphoma	DISSLRAU	Limited	Altered Expression	[12]
Bone osteosarcoma	DIST1004	Limited	Biomarker	[13]
Breast cancer	DIS7DPX1	Limited	Biomarker	[14]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[14]
Gastric cancer	DISXGOUK	Limited	Biomarker	[5]
Kidney cancer	DISBIPKM	Limited	Biomarker	[14]
Lung cancer	DISCM4YA	Limited	Biomarker	[14]
Lung carcinoma	DISTR26C	Limited	Biomarker	[14]
Osteosarcoma	DISLQ7E2	Limited	Biomarker	[13]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[14]
Stomach cancer	DISKIJSX	Limited	Biomarker	[5]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Gefitinib	DM15F0X	Approved	Coronin-1C (CORO1C) affects the response to substance of Gefitinib.	[7]

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 Coronin-1C (CORO1C).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Coronin-1C (CORO1C).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Coronin-1C (CORO1C).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coronin-1C (CORO1C).	[18]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Coronin-1C (CORO1C).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coronin-1C (CORO1C).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Coronin-1C (CORO1C).	[22]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Coronin-1C (CORO1C).	[23]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Coronin-1C (CORO1C).	[23]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Coronin-1C (CORO1C).	[24]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Coronin-1C (CORO1C).	[25]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Coronin-1C (CORO1C).	[27]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Coronin-1C (CORO1C).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Coronin-1C (CORO1C).	[26]

References

• [1] CRN2 binds to TIMP4 and MMP14 and promotes perivascular invasion of glioblastoma cells.Eur J Cell Biol. 2019 Dec;98(5-8):151046. doi: 10.1016/j.ejcb.2019.151046. Epub 2019 Oct 11.
• [2] Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy.J Pathol. 2008 Mar;214(4):415-24. doi: 10.1002/path.2308.
• [3] Coronin 3 negatively regulates G6PC3 in HepG2 cells, as identified by labelfree massspectrometry.Mol Med Rep. 2017 Sep;16(3):3407-3414. doi: 10.3892/mmr.2017.7002. Epub 2017 Jul 15.
• [4] The molecular phenotype of endocapillary proliferation: novel therapeutic targets for IgA nephropathy.PLoS One. 2014 Aug 18;9(8):e103413. doi: 10.1371/journal.pone.0103413. eCollection 2014.
• [5] CORO1C expression is associated with poor survival rates in gastric cancer and promotes metastasis invitro.FEBS Open Bio. 2019 Jun;9(6):1097-1108. doi: 10.1002/2211-5463.12639. Epub 2019 Apr 29.
• [6] Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K.Mol Cancer. 2012 Sep 14;11:67. doi: 10.1186/1476-4598-11-67.
• [7] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.
• [8] Silencing of MALAT1 inhibits migration and invasion by sponging miR??p in prostate cancer cells.Mol Med Rep. 2019 Oct;20(4):3499-3508. doi: 10.3892/mmr.2019.10602. Epub 2019 Aug 22.
• [9] miR-206 inhibits cell migration through direct targeting of the actin-binding protein coronin 1C in triple-negative breast cancer.Mol Oncol. 2014 Dec;8(8):1690-702. doi: 10.1016/j.molonc.2014.07.006. Epub 2014 Jul 12.
• [10] Bivariate Genome-Wide Association Scan Identifies 6 Novel Loci Associated With Lipid Levels and Coronary Artery Disease.Circ Genom Precis Med. 2018 Dec;11(12):e002239. doi: 10.1161/CIRCGEN.118.002239.
• [11] Modifier genes: Moving from pathogenesis to therapy.Mol Genet Metab. 2017 Sep;122(1-2):1-3. doi: 10.1016/j.ymgme.2017.05.018. Epub 2017 May 30.
• [12] Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration.J Pathol. 2010 Oct;222(2):166-79. doi: 10.1002/path.2752.
• [13] Identification of miRNA and genes involving in osteosarcoma by comprehensive analysis of microRNA and copy number variation data.Oncol Lett. 2017 Nov;14(5):5427-5433. doi: 10.3892/ol.2017.6845. Epub 2017 Aug 28.
• [14] miR-26 suppresses renal cell cancer via down-regulating coronin-3.Mol Cell Biochem. 2020 Jan;463(1-2):137-146. doi: 10.1007/s11010-019-03636-2. Epub 2019 Oct 8.
• [15] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [16] Cyclosporine A--induced oxidative stress in human renal mesangial cells: a role for ERK 1/2 MAPK signaling. Toxicol Sci. 2012 Mar;126(1):101-13.
• [17] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [18] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [19] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [20] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [21] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [22] 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.
• [23] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [24] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [25] 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.
• [26] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [27] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [28] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.