Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer

Huang, Xinwei; Zhang, Hong; Guo, Xiaoran; Zhu, Zongxin; Cai, Haibo; Kong, Xiangyang

doi:10.1186/s13045-018-0628-y

Cited by 230 publications

(207 citation statements)

References 100 publications

(156 reference statements)

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“…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) .…”

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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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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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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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“…That post-translational modifications of IGF2BP1 might play a crucial role in regulating the activity of this RBP was also suggested by the findings of Hämmerle and colleagues [64]. They did not observe a negative correlation between the mRNA level of IGF2BP1, which is in fact upregulated rather than downregulated in HCC, and the level of HULC, which is highly elevated in HCC but whose decay was found to be promoted by IGF2BP1 [64,103]. This indicates that the activity of IGF2BP1 might somehow be impeded in HCC by post-translational mechanisms [64,103].…”

Section: Insulin-like Growth Factor 2 Mrna-binding Protein 1 (Igf2bp1)mentioning

confidence: 86%

“…IGF2BP1, together with IGF2BP2 and IGF2BP3, belongs to a family of RBPs that is expressed in embryonic tissue and frequently reactivated in different types of cancers but rarely expressed in normal adult tissue [103,104]. Due to its regulation of stability, localization, and translation of numerous mRNAs like c-Myc [105,106], beta-catenin [107], and KRAS [108], it plays a role in embryogenesis and tumor development [103,104]. IGF2BP1 carries two RRMs in its N-terminal region and four hnRNP-K homology (KH) domains in the C-terminus, which are primarily responsible for its interaction with RNA targets in an N6-methyladenosine (m6A)-dependent manner [103,104].…”

Section: Insulin-like Growth Factor 2 Mrna-binding Protein 1 (Igf2bp1)mentioning

confidence: 99%

“…Due to its regulation of stability, localization, and translation of numerous mRNAs like c-Myc [105,106], beta-catenin [107], and KRAS [108], it plays a role in embryogenesis and tumor development [103,104]. IGF2BP1 carries two RRMs in its N-terminal region and four hnRNP-K homology (KH) domains in the C-terminus, which are primarily responsible for its interaction with RNA targets in an N6-methyladenosine (m6A)-dependent manner [103,104].…”

Section: Insulin-like Growth Factor 2 Mrna-binding Protein 1 (Igf2bp1)mentioning

confidence: 99%

“…Upon trying to understand the mechanism behind this effect, the authors of the study found that IGF2BP1 interacted with CCR4-NOT transcription complex subunit 1 (CNOT1), a component of the deadenylase complex CCR4-NOT, which induces 3 -5 -decay of cytoplasmic RNAs [64]. Interestingly, IGF2BP1 had previously only been known to increase the stability of its RNA targets, as exemplified by c-Myc, which is shielded from the degradation trough endoribonucleases by being sequestered in so-called messenger ribonucleoproteins (mRNPs) that are formed by IGF2BP1 together with various other RBPs [103][104][105][106]. The study by Hämmerle et al was the first to report a destabilizing function exerted by IGF2BP1 [64].…”

Section: Insulin-like Growth Factor 2 Mrna-binding Protein 1 (Igf2bp1)mentioning

confidence: 99%

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RNA-Binding Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

Jonas

Calin

Pichler

2020

IJMS

102

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The majority of the genome is transcribed into pieces of non-(protein) coding RNA, among which long non-coding RNAs (lncRNAs) constitute a large group of particularly versatile molecules that govern basic cellular processes including transcription, splicing, RNA stability, and translation. The frequent deregulation of numerous lncRNAs in cancer is known to contribute to virtually all hallmarks of cancer. An important regulatory mechanism of lncRNAs is the post-transcriptional regulation mediated by RNA-binding proteins (RBPs). So far, however, only a small number of known cancer-associated lncRNAs have been found to be regulated by the interaction with RBPs like human antigen R (HuR), ARE/poly(U)-binding/degradation factor 1 (AUF1), insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), and tristetraprolin (TTP). These RBPs regulate, by various means, two aspects in particular, namely the stability and the localization of lncRNAs. Importantly, these RBPs themselves are commonly deregulated in cancer and might thus play a major role in the deregulation of cancer-related lncRNAs. There are, however, still many open questions, for example regarding the context specificity of these regulatory mechanisms that, in part, is based on the synergistic or competitive interaction between different RBPs. There is also a lack of knowledge on how RBPs facilitate the transport of lncRNAs between different cellular compartments. Compared to protein-coding genes, lncRNAs are poorly conserved between different species and their expression levels are rather low [7,8]. Initially, this led to the belief that they were nothing but transcriptional noise [6][7][8]. Soon, however, it was discovered that lncRNAs do exhibit considerable functionality, for example as regulators of transcription [6][7][8]. Mechanisms of transcriptional regulation by lncRNAs are multifarious and can occur either in cis or in trans, meaning either closer to or further away from the lncRNA's site of transcription, respectively [6,7]. A frequent mechanism of transcriptional regulation via lncRNAs is the recruitment, or prevention of such, of components of chromatin or histone-modifying complexes, like polycomb repressive complexes or histone deacetylase complexes [11][12][13]. LncRNAs can also direct transcription factors or cofactors to promoter regions of genes and facilitate the formation of chromatin loops between distant enhancers and promoters, as observed for some eRNAs [9,[14][15][16][17]. Another way that they can impact transcription is by interfering with the RNA polymerase II transcription machinery, thereby blocking transcriptional initiation or elongation [18]. LncRNAs are important regulators not only at the level of transcription but also at the post-transcriptional level [6,7]. They regulate pre-mRNA splicing by interacting with splicing factors or with the mRNA itself [19][20][21][22]. A well-studied example for this is metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an lncRNA that interacts with serine/arginine (SR) spl...

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Identification and validation of RNA‐binding protein‐related gene signature revealed potential associations with immunosuppression and drug sensitivity in glioma

Chen

Yang

et al. 2021

Cancer Medicine

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Background Glioma is the most common central nervous system tumor in adults, and a considerable part of them are high‐degree ones with high malignancy and poor prognosis. At present, the classification and treatment of glioma are mainly based on its histological characteristics, so studies at the molecular level are needed. Methods RNA‐seq data from The Cancer Genome Atlas (TCGA) datasets (n = 703) and Chinese Glioma Genome Atlas (CGGA) were utilized to find out the differentially expressed RNA‐binding proteins (RBPs) between normal cerebral tissue and glioma. A prediction system for the prognosis of glioma patients based on 11 RBPs was established and validated using uni‐ and multi‐variate Cox regression analyses. STITCH and CMap databases were exploited to identify putative drugs and their targets. Single sample gene set enrichment analysis (ssGSEA) was used to calculate scores of specific immune‐related gene sets. IC50 of over 20,000 compounds in 60 cancer cell lines was collected from the CellMiner database to test the drug sensitivity prediction value of the RBP‐based signature. Results We established a reliable prediction system for the prognosis of glioma patients based on 11 RBPs including THOC3, LSM11, SARNP, PABPC1L2B, SMN1, BRCA1, ZC3H8, DZIP1L, HEXIM2, LARP4B, and ZC3H12B. These RBPs were primarily associated with ribosome and post‐transcriptional regulation. RBP‐based risk scores were closely related to immune cells and immune function. We also confirmed the potential of the signature to predict the drug sensitivity of currently approved or evaluated drugs. Conclusions Differentially expressed RBPs in glioma can be used as a basis for prognosis prediction, new drugs screening and drug sensitivity prediction. As RBP‐based glioma risk scores were associated with immunity, immunotherapy may become an important treatment for glioma in the future.

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Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) in cancer

Cited by 230 publications

References 100 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 Proteins as Important Regulators of Long Non-Coding RNAs in Cancer

Identification and validation of RNA‐binding protein‐related gene signature revealed potential associations with immunosuppression and drug sensitivity in glioma

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