CircPTPRA blocks the recognition of RNA N6-methyladenosine through interacting with IGF2BP1 to suppress bladder
Fei Xie1,2, Chao Huang1, Feng Liu1
1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
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.
Insights
Circular RNA circPTPRA acts as a tumor suppressor in bladder cancer by blocking IGF2BP1
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Circular RNAs (circRNAs) influence bladder cancer (BC) progression.
- IGF2BP1 is a key m6A reader implicated in BC.
Purpose of the Study:
- Identify novel circRNAs regulating IGF2BP1 in BC.
- Explore circRNA regulatory mechanisms and clinical significance in BC.
Main Methods:
- Investigated IGF2BP1 clinical role in BC.
- RNA immunoprecipitation sequencing (RIP-seq) to identify circRNA interactors.
- Evaluated circPTPRA in BC cell lines and xenografts.
- RNA sequencing to identify circPTPRA target genes.
Main Results:
- IGF2BP1 binds circPTPRA in BC cell cytoplasm.
- circPTPRA inhibits BC cell proliferation, migration, and invasion.
- circPTPRA downregulates MYC and FSCN1 expression by interacting with IGF2BP1.
- circPTPRA partially disrupts IGF2BP1's recognition of m6A-modified RNAs.
Conclusions:
- circPTPRA acts as a tumor suppressor in BC.
- circPTPRA inhibits BC progression by blocking IGF2BP1's m6A RNA recognition.
- circPTPRA represents a potential therapeutic target for BC.
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