Last update 01 Nov 2024

IGF2BP3

Last update 01 Nov 2024

Basic Info

Synonyms

CT98, hKOC, IGF-II mRNA-binding protein 3

+ [10]

Introduction

RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (PubMed:29476152). Binds to the 3'-UTR of CD44 mRNA and stabilizes it, hence promotes cell adhesion and invadopodia formation in cancer cells. Binds to beta-actin/ACTB and MYC transcripts. Increases MYC mRNA stability by binding to the coding region instability determinant (CRD) and binding is enhanced by m6A-modification of the CRD (PubMed:29476152). Binds to the 5'-UTR of the insulin-like growth factor 2 (IGF2) mRNAs.

Drugs associated with IGF2BP3

Asudemotide

Target

DEPDC1 x IGF2BP3 x KIF20B x LY6K x NUF2

Mechanism

DEPDC1 inhibitors [+4]

Active Org.

OncoTherapy Science, Inc. [+1]

Originator Org.

OncoTherapy Science, Inc.

Active Indication

Esophageal Carcinoma [+2]

Inactive Indication-

Drug Highest PhasePhase 3

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

S-588210

Target

IGF2BP3 x LY6K x NUF2

Mechanism

IGF2BP3 agonists [+3]

Active Org.

OncoTherapy Science, Inc. [+1]

Originator Org.

OncoTherapy Science, Inc.

Active Indication

Mesothelioma

Inactive Indication

Bladder Cancer [+4]

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CN115746120

Patent Mining

Target

IGF2BP3

Mechanism-

Active Org.

Zhejiang Provincial Peoples Hospital

Originator Org.

Zhejiang Provincial Peoples Hospital

Active Indication

Uterine Cervical Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with IGF2BP3

NCT04106115 / RecruitingPhase 1/2IIT

A Phase Ib/II Study to Assess the Safety and Activity of DURvalumab (MEDI4736) in Combination With S-488210/S-488211 vAccine in Non-muscle Invasive Bladder CancEr

DURANCE is a two part, phase Ib/II, multi-centre study to assess the safety and activity of S-488210/S-488211 in combination with durvalumab, in patients with non-muscle invasive bladder cancer (NMIBC).

Start Date25 Mar 2022

Sponsor / Collaborator

University College London

[+2]

NCT04316689 / CompletedPhase 1

Open-label, Phase 1 Study of S-488210/S-488211 to Evaluate the Safety and Tolerability in Patients With Unresectable Recurrent and/or Metastatic Solid Tumor

The primary objective is to evaluate the safety and tolerability of S-588210 (S-488210+S-488211) in patients with unresectable recurrent and/or metastatic solid tumors.

Start Date30 Jul 2019

Sponsor / Collaborator

Shionogi, Inc.

JPRN-UMIN000023324 / CompletedPhase 1

Exploratory study to determine S-588410-induced tumor infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients - Exploratory study to determine S-588410-induced tumor infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients

Start Date25 Jul 2016

Sponsor / Collaborator

Shionogi & Co., Ltd.

100 Clinical Results associated with IGF2BP3

100 Translational Medicine associated with IGF2BP3

0 Patents (Medical) associated with IGF2BP3

701

Literatures (Medical) associated with IGF2BP3

01 Dec 2024·International Immunopharmacology

IGF2BP3 regulates macrophage-induced inflammation and liver damage in acute-on-chronic liver failure via the RORα-NF-κB signaling axis

Article

Author: Liu, Shu ; Liu, Kai ; Cheng, Ke ; Zhao, Yujun ; Wang, Qiang

Acute-on-chronic liver failure (ACLF) is a severe condition characterized by high mortality rates, and macrophage-mediated inflammation plays a critical role in its progression. Our previous research has indicated the involvement of the RNA-binding protein IGF2BP3 in the pathogenesis of ACLF. However, the underlying molecular mechanisms contributing to this damage require further elucidation. Initially, we observed heightened expression of pro-inflammatory cytokines and macrophage activation in both ACLF patients and a mouse model induced by D-GalN/LPS. Subsequent loss-of-function experiments targeting IGF2BP3 revealed that the knockdown of IGF2BP3 potentially confers hepatoprotection by mitigating macrophage-induced inflammation. Further investigation using RNA Immunoprecipitation (RIP) assays and dual luciferase reporter assays confirmed that RORα is a target protein of the RNA-binding protein IGF2BP3. Importantly, depletion of RORα was found to significantly increase liver damage and inflammation by modulating the NF-κB signaling pathway. In conclusion, our findings underscore the crucial role of IGF2BP3 in mediating liver damage induced by activated macrophages in ACLF, which is regulated by the RORα-NF-κB signaling pathway. These discoveries offer novel insights into the pathogenesis and potential therapeutic targets for ACLF.

01 Dec 2024·Cellular and Molecular Life Sciences

IGF2BP3-mediated enhanced stability of MYLK represses MSC adipogenesis and alleviates obesity and insulin resistance in HFD mice

Article

Author: He, Wuhui ; Fan, Shuai ; Huang, Xiuji ; Ye, Guiwen ; Li, Hui

AbstractMesenchymal stem cells (MSCs) hold immense potential as multipotent stem cells and serve as a primary source of adipocytes. The process of MSC adipogenesis plays a crucial role in maintaining systemic metabolic homeostasis and has garnered significant attention in tissue bioengineering. N6-methyladenosine (m6A), the most prevalent RNA modification, is known to regulate cell fate and disease. However, the precise involvement of m6A readers in MSC adipogenesis remains unclear. In this study, we investigated the impact of IGF2BP3, a prominent m6A reader, on MSC adipogenesis. Our findings revealed a decrease in IGF2BP3 expression during the natural adipogenic differentiation of MSCs. Furthermore, IGF2BP3 was found to repress MSC adipogenesis by augmenting the levels of MYLK, a calcium/calmodulin-dependent kinase. Mechanistically, IGF2BP3 interacted with MYLK mRNA in an m6A-dependent manner, extending its half-life and subsequently inhibiting the phosphorylation of the ERK1/2 pathway, thereby impeding the adipogenic differentiation of MSCs. Additionally, we successfully achieved the overexpression of IGF2BP3 through intraperitoneal injection of adeno-associated virus serotype Rec2, which specifically targeted adipose tissue. This intervention resulted in reduced body weight and improved insulin resistance in high-fat diet mice. Overall, our study provides novel insights into the role of IGF2BP3 in MSC adipogenesis, shedding light on adipocyte-related disorders and presenting potential targets for related biomedical applications.

01 Dec 2024·Molecular Biology Reports

Hypoxia increases the biogenesis of IGF2BP3-bound circular RNAs

Article

Author: Kaushik, Kriti ; Kumar, Hemant ; Mehta, Samriddhi ; Palanichamy, Jayanth Kumar

BACKGROUNDInsulin-like Growth Factor 2 Binding Protein 3 (IGF2BP3) promotes cancer migration and invasion by binding to several coding and non-coding RNAs. Hypoxia stimulates tumor progression by upregulating Hypoxia Inducible Factors and downstream signaling. Quaking (QKI) gene, which is upregulated in hypoxia and promotes epithelial to mesenchymal transition (EMT), induces circular RNAs. Therefore, the axis between IGF2BP3, QKI, circular RNAs and their respective host genes under hypoxia was studied.METHODS AND RESULTSSeveral IGF2BP3-bound circular RNAs were previously identified in HepG2. There were 13 circRNAs originating from 8 host genes bound to IGF2BP3. We confirmed their binding to IGF2BP3 in U87MG using an RNA Immunoprecipitation assay. MALAT1, an oncogenic lncRNA was also found to be associated with IGF2BP3. Three adherent cell lines expressing high levels of IGF2BP3 viz., HeLa, HepG2 and U87MG were cultured under normoxia (20%O₂) and hypoxia (<0.2%O₂) for 48-168 h. Expression of IGF2BP3, QKI, EMT markers, IGF2BP3-bound circRNAs and their host mRNAs expression were assessed by quantitative real-time PCR (qRT-PCR) in both normoxia and hypoxia. The hypoxia markers viz., VEGF and CA9 were upregulated in all the cell lines in hypoxia at all time points along with an increase in SNAIL. We found 6 genes, viz., PHC3, CDYL, ANKRD17, ARID1A, NEIL3 and FNDC3B with increased expression both at the mRNA and circRNA level indicating their synergistic role in tumor initiation. Overall, we found that circRNA to mRNA expression was observed to be increased for most of the genes and time points of hypoxia in all the cell lines. IGF2BP3 and QKI were also upregulated in hypoxia indicating their role in circRNA biogenesis and stability.CONCLUSIONOur data implies that hypoxia augments circRNA biogenesis which might subsequently play a role in tumor progression.

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IGF2BP3

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