Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an important protumorigenic factor in hepatocellular carcinoma

Gutschner, Tony; Haemmerle, Monika; Pazaitis, Nikolaos; Bley, Nadine; Fiškin, Evgenij; Uckelmann, Hannah J.; Heim, Andreas; Groβ, Matthias; Hofmann, Nina; Geffers, Robert; Skawran, Britta; Longerich, Thomas; Breuhahn, Kai; Schirmacher, Peter; Mühleck, Britta; Hüttelmaier, Stefan; Diederichs, Sven

doi:10.1002/hep.26997

Cited by 164 publications

(175 citation statements)

References 50 publications

(70 reference statements)

Supporting

Mentioning

162

Contrasting

Unclassified

Order By: Relevance

“…As described previously, the binding of IGF2BP1 to c-MYC and MKI67 mRNA prevented mRNA degradation and increased mRNA expression (17)(18)(19); the stabilization of CD44 mRNA was attributed to the 3Ј-UTR of the transcript, which was bound by IGF2BP1 protein (20); PTEN mRNA was identified as a novel target transcript of IGF2BP1 and decayed faster in cells upon IGF2BP1 knockdown (21). To verify that the down-regulation of IGF2BP1 expression due to the up-regulation of miR-873 in GBM cells could destabilize c-MYC, MKI67, CD44, and PTEN mRNA, we measured the mRNA levels of these potential target transcripts of IGF2BP1.…”

Section: High Level Of Mir-873 Decreased the Mrna Level Of Mki67 C-msupporting

confidence: 65%

“…IGF2BP1 prevented c-MYC mRNA degradation by binding to the coding region determinant located at the open reading frame and prolonged the half-life of CD44 mRNA by associating with the 3Ј-untranslated region of the transcript (20). Two novel target transcripts of IGF2BP1 protein, PTEN and MARK4, were discovered using a comparative microarray and verified using quantitative RT-PCR (17). Recently, researchers reported that IGF2BP1 stabilized c-MYC and MKI67 mRNAs and enhanced the expression of c-MYC and Ki-67 protein, which are both potent regulators of cell proliferation and apoptosis (17).…”

Section: Discussionmentioning

confidence: 96%

“…Two novel target transcripts of IGF2BP1 protein, PTEN and MARK4, were discovered using a comparative microarray and verified using quantitative RT-PCR (17). Recently, researchers reported that IGF2BP1 stabilized c-MYC and MKI67 mRNAs and enhanced the expression of c-MYC and Ki-67 protein, which are both potent regulators of cell proliferation and apoptosis (17). In our study, the expression of IGF2BP1 target transcripts, including MKI67, c-MYC, PTEN, and CD44 mRNA, was down-regulated after the transfection of GBM cells with miR-873 mimics (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

MicroRNA-873 (MiRNA-873) Inhibits Glioblastoma Tumorigenesis and Metastasis by Suppressing the Expression of IGF2BP1

Wang

Bao

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Recent research has uncovered tumor-suppressive and oncogenic potential of miRNAs. Results: miR-873 suppresses the proliferation, migration, and invasiveness of GBM cells by targeting IGF2BP1. Conclusion: Down-regulation of miR-873 results in overexpressed IGF2BP1, contributing to tumorigenesis of GBM cells. Significance: The identification of tumor suppressor miR-873 and its oncogenic target IGF2BP1 in GBM cells is potentially valuable for cancer diagnosis and therapy.

show abstract

Section: High Level Of Mir-873 Decreased the Mrna Level Of Mki67 C-msupporting

confidence: 65%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA-873 (MiRNA-873) Inhibits Glioblastoma Tumorigenesis and Metastasis by Suppressing the Expression of IGF2BP1

Wang

Bao

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…They also show that high CRD-BP expression levels correlated with poor patient outcomes. A recent study (26) employing an Agilent microarray platform showed that CRD-BP/IGF2BP1 is expressed in adult liver. This study utilized PCR primers directed to sequences in exon 11 to confirm the gene expression changes observed for hepatocellular tumors; we predict that this assay would capture the majority of mRNA isoforms (equivalent to our total CRD-BP assay with qRT-PCR primers targeting a region in exon 15).…”

Section: Discussionmentioning

confidence: 99%

Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells

Fakhraldeen

Clark

Roopra

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The RNA binding protein, coding region determinant-binding protein (CRD-BP), is expressed by tumor cells and protects key mRNAs. Results: This study identifies a novel variant of CRD-BP and finds that CRD-BP is required for breast tumor cell clonogenicity. Conclusion: CRD-BP has tumorigenic activity and is ubiquitously expressed in breast epithelium. Significance: Under-reporting of CRD-BP isoforms suggests that published studies may be incomplete.

show abstract

“…The overexpression of IGF2BP1 not only enhances the velocity of cell motility but also promotes the directionality of migration (7). A high level of IGF2BP1 expression enhances the migratory and invasive potential of cells and promotes their proliferation (8). IGF2BP family members are essential for the migration of neural crest cells and the central regulation of the properties of stem cells within the LIN28/Let-7 networks (9,10).…”

mentioning

confidence: 99%

Potential proteins targeted by let-7f-5p in HeLa cells

Wang¹,

Chen²,

Zhang³

et al. 2017

BST

View full text Add to dashboard Cite

MicroRNAs (miRNAs) are a class of endogenous, nonprotein coding RNAs that are small (approximately 22 nucleotides in length) and highly conserved. MiRNAs have a widespread impact on regulation of gene expression and evolution and are thought to affect over 50% of all human genes (1). let-7 miRNA was originally identified in Caenorhabditis elegans (C. elegans) as a regulator of developmental timing and cell proliferation (2). The let-7 family is a particularly interesting example as one of the few families that are also conserved in Drosophila and C. elegans. In humans, the let-7 family consists of 9 mature let-7 miRNAs encoded by 12 different genomic loci, some of which are clustered together.let-7f, which is a member of the let-7 family, is located at 9q22.3. More importantly, let-7f is a novel regulator in human endocervical cells and is involved in the induction of immune tolerance (3). let-7f was found to play an important role in cell growth, migration, invasion, and angiogenesis in tumors (4). The aim of the current study was to investigate the relationship between let-7f-5p and the genes it potentially targets at the protein level in vitro.Five thousand and fifty-two proteins were identified from 31,666 peptides at a minimum confidence level of 95%. Results identified 164 proteins that were expressed at significantly different levels in HeLa cells overexpressing let-7f-5p, including 59 proteins that were up-regulated (1.5-fold, p < 0.5) and 105 proteins that were down-regulated (1.5-fold, p < 0.5). One hundred and seventy-two proteins were identified in let-7f-5p-inhibited HeLa cells, including 44 proteins that were up-regulated (1.5-fold, p < 0.5) and 128 proteins that were down-regulated (1.5-fold, p < 0.5). Expression of IGF2BP1, vimentin, Keratin, and Protein FAM decreased while expression of Integrinα1 increased in HeLa cells overexpressing let7f-5p. In let-7f-5p-silenced HeLa cells, expression of IGF2BP1 and Integrin α1 increased while expression of vimentin and T-complex protein decreased. KEGG analysis revealed that 4 biological pathways including arrhythmogenic right ventricular cardiomyopathy, pyrimidine metabolism, RNA degradation, and the pentose phosphate pathway differed significantly in HeLa cells overexpressing let-7f-5p and that three pathways including glycolysis, alanine, aspartate and glutamate metabolism, and the spliceosome pathway differed significantly in let-7f-5p-silenced HeLa cells.Study data revealed that let-7f-5p overexpression dramatically suppressed IGF2BP1 and vimentin, thus possibly regulating cell migration and invasion in vitro. Moreover, let-7f-5p inhibitors significantly upregulated the expression of IGF2BP1 (Table 1)

show abstract

Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an important protumorigenic factor in hepatocellular carcinoma

Abstract: The RNA-binding protein IGF2BP1 is an important protumorigenic factor in liver carcinogenesis. Hence, therapeutic targeting of IGF2BP1 may offer options for intervention in human HCC.

Cited by 164 publications

References 50 publications

MicroRNA-873 (MiRNA-873) Inhibits Glioblastoma Tumorigenesis and Metastasis by Suppressing the Expression of IGF2BP1

MicroRNA-873 (MiRNA-873) Inhibits Glioblastoma Tumorigenesis and Metastasis by Suppressing the Expression of IGF2BP1

Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells

Potential proteins targeted by let-7f-5p in HeLa cells

Contact Info

Product

Resources

About