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Title:
CircPTPRA blocks the recognition of RNA N6-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression | Molecular Cancer
Description:
Background Circular RNAs (circRNAs) have been found to have significant impacts on bladder cancer (BC) progression through various mechanisms. In this study, we aimed to identify novel circRNAs that regulate the function of IGF2BP1, a key m6A reader, and explore the regulatory mechanisms and clinical significances in BC. Methods Firstly, the clinical role of IGF2BP1 in BC was studied. Then, RNA immunoprecipitation sequencing (RIP-seq) analysis was performed to identify the circRNAs interacted with IGF2BP1 in BC cells. The overall biological roles of IGF2BP1 and the candidate circPTPRA were investigated in both BC cell lines and animal xenograft studies. Subsequently, we evaluated the regulation effects of circPTPRA on IGF2BP1 and screened out its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circPTPRA might act as a blocker in recognition of m6A. Results We demonstrated that IGF2BP1 was predominantly binded with circPTPRA in the cytoplasm in BC cells. Ectopic expression of circPTPRA abolished the promotion of cell proliferation, migration and invasion of BC cells induced by IGF2BP1. Importantly, circPTPRA downregulated IGF2BP1-regulation of MYC and FSCN1 expression via interacting with IGF2BP1. Moreover, the recognition of m6A-modified RNAs mediated by IGF2BP1 was partly disturbed by circPTPRA through its interaction with KH domains of IGF2BP1. Conclusions This study identifies exonic circular circPTPRA as a new tumor suppressor that inhibits cancer progression through endogenous blocking the recognition of IGF2BP1 to m6A-modified RNAs, indicating that circPTPRA may serve as an exploitable therapeutic target for patients with BC.
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Keywords {🔍}
igfbp, circptpra, cells, pubmed, article, rna, cell, expression, fig, cancer, google, scholar, myc, cas, overexpression, invasion, fscn, bladder, transfected, mrna, assay, central, migration, analysis, circular, tissues, assays, data, circrnas, control, tumor, protein, zhang, rnas, regulation, images, performed, proliferation, vitro, stably, significantly, progression, study, patients, usa, cycle, results, growth, stability, mrnas,
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aff4/nf-κb/myc signaling network hsa-mir-145-zeb1/2-fscn1 pathway tumor volume = π/6 × length×width2 article download pdf mir-182-5p/p27 axis [12] mir-182-5p/p27 axis protein-coding transcripts region protease/phosphatase inhibitor cocktail small interference rnas igf2 mrna-binding proteins imp-1 displays cross-talk flag-tagged full-length cytoplasmic protein–rna complexes cd31-positive intratumoral microvessels positive feed-back regulation m6a-modified rnas mediated c-myc mrna decay rna–protein binding mixture rna n6-methyladenosine methyltransferase mapk signaling transduction kaplan-meier curves indicating increasing rna-sequencing analyses downstream m6a-modified mrnas surprisingly long half-life flag-tagged igf2bp1 protein promotes cap-independent translation fscn1 mrna half-life lncrna lin28b-as1 canonical rna-binding domains distinct rna-binding domains kaplan–meier survival curve 200 μl serum-free medium impairing mirna-directed downregulation underlying molecular mechanisms cy3-labeled circptpra probes invasive bladder cancer noubissi fk igf2bp1-mediated gene regulation important tumor suppressor igf2bp1 single-guide rna igf2bp1-overexpressed xenograft tumors lin28b mrna stability human bladder cancer 6-methyladenosine search search real-time pcr crd-bp mediates stabilization mrna decay assay m6a-dependent binding mode c-myc mrna stability promotes cancer proliferation
Questions {❓}
- The evolution of bladder cancer genomics: what have we learned and how can we use it?
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headline:CircPTPRA blocks the recognition of RNA N6-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression
description:Circular RNAs (circRNAs) have been found to have significant impacts on bladder cancer (BC) progression through various mechanisms. In this study, we aimed to identify novel circRNAs that regulate the function of IGF2BP1, a key m6A reader, and explore the regulatory mechanisms and clinical significances in BC. Firstly, the clinical role of IGF2BP1 in BC was studied. Then, RNA immunoprecipitation sequencing (RIP-seq) analysis was performed to identify the circRNAs interacted with IGF2BP1 in BC cells. The overall biological roles of IGF2BP1 and the candidate circPTPRA were investigated in both BC cell lines and animal xenograft studies. Subsequently, we evaluated the regulation effects of circPTPRA on IGF2BP1 and screened out its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circPTPRA might act as a blocker in recognition of m6A. We demonstrated that IGF2BP1 was predominantly binded with circPTPRA in the cytoplasm in BC cells. Ectopic expression of circPTPRA abolished the promotion of cell proliferation, migration and invasion of BC cells induced by IGF2BP1. Importantly, circPTPRA downregulated IGF2BP1-regulation of MYC and FSCN1 expression via interacting with IGF2BP1. Moreover, the recognition of m6A-modified RNAs mediated by IGF2BP1 was partly disturbed by circPTPRA through its interaction with KH domains of IGF2BP1. This study identifies exonic circular circPTPRA as a new tumor suppressor that inhibits cancer progression through endogenous blocking the recognition of IGF2BP1 to m6A-modified RNAs, indicating that circPTPRA may serve as an exploitable therapeutic target for patients with BC.
datePublished:2021-04-14T00:00:00Z
dateModified:2022-11-01T00:00:00Z
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Bladder cancer
circPTPRA
IGF2BP1
N
-methyladenosine
Cancer Research
Oncology
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headline:CircPTPRA blocks the recognition of RNA N6-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression
description:Circular RNAs (circRNAs) have been found to have significant impacts on bladder cancer (BC) progression through various mechanisms. In this study, we aimed to identify novel circRNAs that regulate the function of IGF2BP1, a key m6A reader, and explore the regulatory mechanisms and clinical significances in BC. Firstly, the clinical role of IGF2BP1 in BC was studied. Then, RNA immunoprecipitation sequencing (RIP-seq) analysis was performed to identify the circRNAs interacted with IGF2BP1 in BC cells. The overall biological roles of IGF2BP1 and the candidate circPTPRA were investigated in both BC cell lines and animal xenograft studies. Subsequently, we evaluated the regulation effects of circPTPRA on IGF2BP1 and screened out its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circPTPRA might act as a blocker in recognition of m6A. We demonstrated that IGF2BP1 was predominantly binded with circPTPRA in the cytoplasm in BC cells. Ectopic expression of circPTPRA abolished the promotion of cell proliferation, migration and invasion of BC cells induced by IGF2BP1. Importantly, circPTPRA downregulated IGF2BP1-regulation of MYC and FSCN1 expression via interacting with IGF2BP1. Moreover, the recognition of m6A-modified RNAs mediated by IGF2BP1 was partly disturbed by circPTPRA through its interaction with KH domains of IGF2BP1. This study identifies exonic circular circPTPRA as a new tumor suppressor that inhibits cancer progression through endogenous blocking the recognition of IGF2BP1 to m6A-modified RNAs, indicating that circPTPRA may serve as an exploitable therapeutic target for patients with BC.
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Bladder cancer
circPTPRA
IGF2BP1
N
-methyladenosine
Cancer Research
Oncology
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