The Roles of Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 in Cancer and Cancer Stem Cells

Cao, Junguo; Mu, Qingchun; Huang, Haiyan

doi:10.1155/2018/4217259

Cited by 127 publications

(139 citation statements)

References 146 publications

(250 reference statements)

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“…Table 5) and could be involved in circRNA nuclear export or otherwise in circRNA localization. For instance, the IGF2BPs, which we found on average have more target sites in circularizing exons, are regulators of essential mRNAs in tumorigenesis and are important players of mRNA stability and transportation to subcellular compartments (59) . Accordingly, IGF2BP3 was found to bind to several circRNAs (29) .…”

Section: Discussionmentioning

confidence: 80%

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Transcriptome-wide profiles of circular RNA and RNA binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression

Okholm

Sathe

Park

et al. 2020

Preprint

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Circular RNAs (circRNAs) are stable, often highly expressed RNA transcripts with potential to modulate other regulatory RNAs. A few circRNAs have been shown to bind RNA binding proteins (RBPs), however, little is known about the prevalence and strength of these interactions in different biological contexts. Here, we comprehensively evaluate the interplay between circRNAs and RBPs in the ENCODE cell lines, HepG2 and K562, by profiling the expression of circRNAs in fractionated total RNA-sequencing samples and analyzing binding sites of 150 RBPs in large eCLIP data sets. We show that KHSRP binding sites are enriched in flanking introns of circRNAs in both HepG2 and K562 cells, and that KHSRP depletion affects circRNA biogenesis. Additionally, we show that exons forming circRNAs are generally enriched with RBP binding sites compared to non-circularizing exons. To detect individual circRNAs with regulatory potency, we computationally identify circRNAs that are highly covered by RBP binding sites and experimentally validate circRNA-RBP interactions by RNA immunoprecipitations. We characterize circCDYL, a highly expressed circRNA with clinical and functional implications in bladder cancer, which is covered with GRWD1 binding sites. We confirm that circCDYL binds GRWD1 in vivo and functionally characterizes the effect of circCDYL-GRWD1 interactions on target genes in HepG2. Furthermore, we confirm interactions between circCDYL and RBPs in bladder cancer cells and demonstrate that circCDYL depletion affects hallmarks of cancer and perturbs the expression of key cancer genes, e.g. TP53 and MYC . Finally, we show that elevated levels of highly RBP-covered circRNAs, including circCDYL, are associated with overall survival of bladder cancer patients. Our study demonstrates transcriptome-wide and cell-type-specific circRNA-RBP interactions that could play important regulatory roles in tumorigenesis.

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Section: Discussionmentioning

confidence: 80%

“…CircCDYL has been suggested to suppress cell growth by inhibiting MYC protein expression levels in bladder cancer through an unknown mechanism (58) . IGF2BP1 and IGF2BP2 possess oncogenic roles and positively regulate the expression of various oncogenes (reviewed in (50,59) ). We evaluated how circCDYL and RBP depletion affect 50 hallmarks of cancer (60) .…”

mentioning

confidence: 99%

Transcriptome-wide profiles of circular RNA and RNA binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression

Okholm

Sathe

Park

et al. 2020

Preprint

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“…[3,9a,b] Recent studies have documented many maternal proteins in mice, including YAP1, MED13, and TLE6, as having essential functions during ZGA. [15,16] IMP2 regulates RNA trafficking, the processing of transcripts that encode key subunits in mitochondrial respiratory chain complexes, and IGF2 mRNA translation. [12,13] IMP2 has two RNA-recognizing motifs and four KH domains that control its binding specificity for RNA.…”

Section: Introductionmentioning

confidence: 99%

RNA‐Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation

et al. 2019

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A number of genes involved in zygotic genome activation (ZGA) have been identified, but the RNA‐binding maternal factors that are directly related to ZGA in mice remain unclear. The present study shows that maternal deletion of Igf 2bp2 (also commonly known as Imp2 ) in mouse embryos causes early embryonic developmental arrest in vitro at the 2‐cell‐stage. Transcriptomics and proteomics analyses of 2‐cell‐stage embryos in mice reveal that deletion of IMP2 downregulates the expression of Ccar1 and Rps14 , both of which are required for early embryonic developmental competence. IGF2, a target of IMP2, when added in culture media, increases the proportion of wild‐type embryos that develop successfully to the blastocyst stage: from 29% in untreated controls to 65% (50 × 10 −9 m IGF2). Furthermore, in an experiment related to embryo transfer, foster mothers receiving IGF2‐treated embryos deliver more pups per female than females who receive untreated control embryos. In clinically derived human oocytes, the addition of IGF2 to the culture media significantly enhances the proportion of embryos that develop successfully. Collectively, the findings demonstrate that IMP2 is essential for the regulation and activation of genes known to be involved in ZGA and reveal the potential embryonic development‐related utility of IGF2 for animal biotechnology and for assisted reproduction in humans.

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“…8 Recently, some case-control studies have focused on the relationship of IGFBP3 and IGF1 single nucleotide polymorphisms (SNPs) with the risk of cancer. 19,20 Dai et al 21 reported that IGF2BP2 is a tumor promoter, which drives tumor proliferation through HMGA1 and mRNAs IGF2. 12 Also, significant association with the survival of breast cancer in Chinese premenopausal women was identified for IGFBP3 rs3110697 G > A.…”

Section: Introductionmentioning

confidence: 99%

Investigation of IGF1, IGF2BP2, and IGFBP3 variants with lymph node status and esophagogastric junction adenocarcinoma risk

Tang

Chen

Liu

et al. 2018

J of Cellular Biochemistry

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Esophagogastric junction adenocarcinoma (EGJA) may be associated with obesity and overweight. Thus, any variant in energy metabolism–related gene may influence the development of EGJA. In this study, we recruited 720 EGJA cases and 1541 noncancer controls. We selected IGF2BP2 rs4402960 G > T, rs1470579 A > C, IGF1 rs5742612 A > G and IGFBP3 rs3110697 G > A, rs2270628 C > T and rs6953668 G > A loci and assessed the relationship of these polymorphisms with lymph node status and susceptibility of EGJA. We found that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms were associated with the decreased risk of EGJA ( IGF2BP2 rs1470579: CC vs AA: adjusted odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.43‐0.98, P = 0.041 and CC vs AA/AC: adjusted OR = 0.62, 95% CI = 0.41‐0.93, P = 0.021 and IGFBP3 rs6953668: GA vs GG: adjusted OR = 0.66, 95% CI = 0.47‐0.93, P = 0.019 and GA/AA vs GG: adjusted OR = 0.68, 95% CI = 0.48‐0.95, P = 0.026). However, we also found that IGF1 rs5742612 A > G polymorphism increased the risk of LNM among patients with EGJA (GG vs AA: adjusted OR = 1.88, 95% CI = 1.02‐3.46, P = 0.042 and GG vs AA/AG: adjusted OR = 1.92, 95% CI = 1.06‐3.47, P = 0.032). This study suggests that IGF2BP2 rs1470579 A > C and IGFBP3 rs6953668 G > A polymorphisms may decrease genetic susceptibility to EGJA in eastern Chinese Han population. In addition, our findings also indicate that IGF1 rs5742612 A > G polymorphism may increase the susceptibility of LNM among patients with EGJA.

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The Roles of Insulin-Like Growth Factor 2 mRNA-Binding Protein 2 in Cancer and Cancer Stem Cells

Cited by 127 publications

References 146 publications

Transcriptome-wide profiles of circular RNA and RNA binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression

Transcriptome-wide profiles of circular RNA and RNA binding protein interactions reveal effects on circular RNA biogenesis and cancer pathway expression

RNA‐Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation

Investigation of IGF1, IGF2BP2, and IGFBP3 variants with lymph node status and esophagogastric junction adenocarcinoma risk

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