m6A Regulator Information

General Information of the m6A Regulator (ID: REG00030)
Regulator Name Insulin-like growth factor-binding protein 3 (IGFBP3)
Synonyms
IGFBP3; IBP3; IBP-3; IGF-binding protein 3; IGFBP-3
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Gene Name IGFBP3
Sequence
MQRARPTLWAAALTLLVLLRGPPVARAGASSAGLGPVVRCEPCDARALAQCAPPPAVCAE
LVREPGCGCCLTCALSEGQPCGIYTERCGSGLRCQPSPDEARPLQALLDGRGLCVNASAV
SRLRAYLLPAPPAPGNASESEEDRSAGSVESPSVSSTHRVSDPKFHPLHSKIIIIKKGHA
KDSQRYKVDYESQSTDTQNFSSESKRETEYGPCRREMEDTLNHLKFLNVLSPRGVHIPNC
DKKGFYKKKQCRPSKGRKRGFCWCVDKYGQPLPGYTTKGKEDVHCYSMQSK
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Function
IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R. Inhibits the positive effect of humanin on insulin sensitivity . Promotes testicular germ cell apoptosis.
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Gene ID 3486
Uniprot ID
IBP3_HUMAN
Regulator Type WRITER ERASER READER
Mechanism Diagram Click to View the Original Diagram
Full List of Target Gene(s) of This m6A Regulator and Corresponding Disease/Drug Response(s)
IGFBP3 can regulate the m6A methylation of following target genes, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulted from the regulation of certain target gene.
Browse Target Gene related Disease
Browse Target Gene related Drug
Thrombospondin-1 (THBS1)
 Target Gene 
Representative RNA-seq result indicating the expression of this target gene regulated by IGFBP3
Cell Line SAS cell line Homo sapiens
Treatment: siIGFBP3 SAS cells
Control: siControl SAS cells
 GSE205275
Regulation
logFC: -1.19E+00
p-value: 1.58E-03
More Results Click to View More RNA-seq Results
Malignant mixed epithelial mesenchymal tumour [ICD-11: 2B5D]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [1]
Responsed Disease Malignant mixed epithelial mesenchymal tumour of ovary [ICD-11: 2B5D.0]
Cell Process Cell proliferation
In-vitro Model
 OVTW59 (Ovarian cancer cell line)
OVTW59-P0 (Ovarian cancer cell line sub-lines)
OVTW59-P4 (Ovarian cancer cell line sub-lines)
A-549 Lung adenocarcinoma Homo sapiens CVCL_0023
NCI-H1299 Lung large cell carcinoma Homo sapiens CVCL_0060
HEK293T Normal Homo sapiens CVCL_0063
In-vivo Model Severe combined immunodeficiency (SCID) female mice aged 6-8 weeks were transplanted subcutaneously with 2 × 107 P4-pBIG2i-hIGFBP3 or P4-pBIG2i transfectant cells. Tumor growth was measured using Vernier calipers and the volume was calculated using the formula: length × width × width × 0.52, which approximates the volume of an elliptical solid mass. Doxycycline at 2 mg/mL in drinking water with 2% sucrose was used to feed the animals when the tumor size was over 0.5 cm in diameter. The xenograft tumors were removed from five animals from each group on days 4, 7, 11, 14, and 20 after doxycycline treatment.
Response Summary IGFBP3 was shown to function as a suppressor of invasion in epithelial ovarian cancer (EOC). IGFBP3 could activate Thrombospondin-1 (THBS1) through promoter regulation mainly via an intracellular signaling pathway, such angiogenesis-regulating ability represents a major function of IGFBP3 as an onco-suppressor in the pathogenesis of ovarian cancer.
Insulin-like growth factor I (IGF1)
 Target Gene 
Lung cancer [ICD-11: 2C25]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [2]
Responsed Disease Lung cancer [ICD-11: 2C25]
Responsed Drug Cisplatin Approved
 Drug Info 
Pathway Response MAPK signaling pathway hsa04010
Cell Process Cell apoptosis
In-vitro Model
 NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
HCC2429 Lung non-small cell carcinoma Homo sapiens CVCL_5132
In-vivo Model Paired littermates of F2 (Igfbp3+/+:KrasG12D/+ and Igfbp3-/-:KrasG12D/+) were sacrificed ranging from ages 4 to 7 months. After preliminary analysis of F2 mice, we sacrificed 5-month-old Igfbp3+/+:KrasG12D/+ and Igfbp3-/-KrasG12D/+ mice that had been backcrossed to S129 background for representative analysis. The lung tissue was immediately removed after the mice were sacrificed and visible pleural nodules were counted directly.
Response Summary overexpression of IGFBP3 induced apoptosis and enhanced cisplatin response in vitro and confirmed that the suppression is in part by blocking Insulin-like growth factor I (IGF1) signaling. IGFBP3 is effective in lung cancer cells with high IGF1 signaling activity and imply that relevant biomarkers are essential in selecting lung cancer patients for IGF1-targeted therapy.
Myc proto-oncogene protein (MYC)
 Target Gene 
Brain cancer [ICD-11: 2A00]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [3]
Responsed Disease Glioblastoma [ICD-11: 2A00.00]
In-vitro Model
 ENSA (A human embryonic stem derived neural progenitor cell)
HNP1 (A human neural progenitor cell)
NSC11 (Pluripotent derived neural progenitor cell)
NHA (Normal human astrocytes)
In-vivo Model Implanting 5000 human derived GSCs into the right cerebral cortex of NSG mice at a depth of 3.5 mm under a University of California, San Diego Institutional Animal Care and Use Committee (IACUC) approved protocol. Brains were harvested and fixed in 4% formaldehyde, cryopreserved in 30% sucrose, and then cryosectioned. Hematoxylin and eosin (H&E) staining was performed on sections for histological analysis. In parallel survival experiments, mice were observed until the development of neurological signs. For in vivo drug treatment studies, intracranial xenografts were generated by implanting 5000 patient-derived GSCs (387 and 4121) into the right cerebral cortex of NSG mice as described above. Mice recovered for 7 days were randomly assigned into drug vs. treatment group by a blinded investigator. Mice were then treated daily with either vehicle (25 mM Tartaric acid) or 50 mg/kg linsitinib by oral gavage.
Response Summary YTHDF2 depletion downregulated IGFBP3 mRNA and protein levels, without affecting its mRNA stability. YTHDF2 regulated IGFBP3 levels via Myc proto-oncogene protein (MYC) in glioblastoma stem cells.
Vascular cell adhesion protein 1 (VCAM1)
 Target Gene 
Osteosarcoma [ICD-11: 2B51]
In total 1 item(s) under this disease
 Disease Info 
Experiment 1 Reporting the m6A-centered Disease Response of This Target Gene [4]
Responsed Disease Osteosarcoma [ICD-11: 2B51]
Pathway Response PI3K-Akt signaling pathway hsa04151
In-vitro Model
 MG-63 Osteosarcoma Homo sapiens CVCL_0426
U2OS Osteosarcoma Homo sapiens CVCL_0042
Response Summary higher IGFBP-3 levels in osteosarcoma tissue compared with normal healthy tissue. IGFBP-3 treatment of two human osteosarcoma cell lines promoted cell migration and upregulated levels of Vascular cell adhesion protein 1 (VCAM1) expression via PI3K/Akt and AP-1 signaling.
Insulin-like growth factor I (IGF1)
 Target Gene 
Cisplatin [Approved]
In total 1 item(s) under this drug
 Drug Info 
Experiment 1 Reporting the m6A-centered Drug Response of This Target Gene [2]
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response MAPK signaling pathway hsa04010
Cell Process Cell apoptosis
In-vitro Model NCI-H460 Lung large cell carcinoma Homo sapiens CVCL_0459
HCC2429 Lung non-small cell carcinoma Homo sapiens CVCL_5132
In-vivo Model Paired littermates of F2 (Igfbp3+/+:KrasG12D/+ and Igfbp3-/-:KrasG12D/+) were sacrificed ranging from ages 4 to 7 months. After preliminary analysis of F2 mice, we sacrificed 5-month-old Igfbp3+/+:KrasG12D/+ and Igfbp3-/-KrasG12D/+ mice that had been backcrossed to S129 background for representative analysis. The lung tissue was immediately removed after the mice were sacrificed and visible pleural nodules were counted directly.
Response Summary overexpression of IGFBP3 induced apoptosis and enhanced cisplatin response in vitro and confirmed that the suppression is in part by blocking Insulin-like growth factor I (IGF1) signaling. IGFBP3 is effective in lung cancer cells with high IGF1 signaling activity and imply that relevant biomarkers are essential in selecting lung cancer patients for IGF1-targeted therapy.
Click to View Potential Drug Response of This Regulator
Xenobiotics Compound(s) Regulating the m6A Methylation Regulator
Compound Name PMID30298385-Compound-scFv B7J Investigative
Description
scFv B7J showed better binding to IGFBP2 at its carboxy terminal domain, blocked IGFBP2-cell surface association, reduced activity of matrix metalloprotease 2 in the conditioned medium of glioma cells and inhibited IGFBP2 induced migration and invasion of glioma cells.
 [5]
References
Ref 1 IGFBP3 inhibits angiogenesis through intracellular regulation of THBS1 expression. Am J Cancer Res. 2020 Jun 1;10(6):1728-1744. eCollection 2020.
Ref 2 IGFBP3 Modulates Lung Tumorigenesis and Cell Growth through IGF1 Signaling. Mol Cancer Res. 2017 Jul;15(7):896-904. doi: 10.1158/1541-7786.MCR-16-0390. Epub 2017 Mar 22.
Ref 3 The RNA m6A Reader YTHDF2 Maintains Oncogene Expression and Is a Targetable Dependency in Glioblastoma Stem Cells. Cancer Discov. 2021 Feb;11(2):480-499. doi: 10.1158/2159-8290.CD-20-0331. Epub 2020 Oct 6.
Ref 4 IGFBP-3 stimulates human osteosarcoma cell migration by upregulating VCAM-1 expression. Life Sci. 2021 Jan 15;265:118758. doi: 10.1016/j.lfs.2020.118758. Epub 2020 Nov 12.
Ref 5 The combination of everolimus and terameprocol exerts synergistic antiproliferative effects in endometrial cancer: molecular role of insulin-like growth factor binding protein 2. J Mol Med (Berl). 2018 Nov;96(11):1251-1266. doi: 10.1007/s00109-018-1699-5. Epub 2018 Oct 8.