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REMR: Identification of RNA Editing-mediated MiRNA Regulation in Cancers
Xu Zhou1, Haizhou Liu2, Fei Hou1
1Department of Biomedical Engineering, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China.
Abstract:
Dysregulation of adenosine-to-inosine (A-to-I) RNA editing has been implicated in cancer progression. However, a comprehensive understanding of how A-to-I RNA editing is incorporated into miRNA regulation to modulate gene expression in cancer remains unclear, given the lack of effective identification methods. To this end, we introduced an information theory-based algorithm named REMR to systematically identify 12,006 A-to-I RNA editing-mediated miRNA regulatory triplets (RNA editing sites, miRNAs, and genes) across ten major cancer types based on multi-omics profiling data from The Cancer Genome Atlas (TCGA). Through analyses of functional enrichment, transcriptional regulatory networks, and protein-protein interaction (PPI) networks, we showed that RNA editing-mediated miRNA regulation potentially affects critical cancer-related functions, such as apoptosis, cell cycle, drug resistance, and immunity. Furthermore, triplets can serve as biomarkers for classifying cancer subtypes with distinct prognoses or drug responses, highlighting the clinical relevance of such regulation. In addition, an online resource (http://www.jianglab.cn/REMR/) was constructed to support the convenient retrieval of our findings. In summary, our study systematically dissected the RNA editing-mediated miRNA regulations, thereby providing a valuable resource for understanding the mechanism of RNA editing as an epitranscriptomic regulator in cancer.
Insights
Adenosine-to-inosine (A-to-I) RNA editing influences microRNA (miRNA) regulation in cancer. Our study identified 12,006 RNA editing-mediated miRNA regulatory triplets, revealing their role in cancer progression and potential as biomarkers.
Area of Science:
- Epitranscriptomics
- Cancer Biology
- Bioinformatics
Background:
- Dysregulation of adenosine-to-inosine (A-to-I) RNA editing is linked to cancer progression.
- The interplay between A-to-I RNA editing and microRNA (miRNA) regulation in cancer gene expression is not fully understood.
- Effective methods for identifying these regulatory interactions are lacking.
Purpose of the Study:
- To systematically identify A-to-I RNA editing-mediated miRNA regulatory triplets in ten major cancer types.
- To investigate the functional roles and clinical relevance of these regulatory interactions.
- To provide a comprehensive resource for studying RNA editing in cancer.
Main Methods:
- Development of an information theory-based algorithm (REMR) for identifying RNA editing-mediated miRNA regulatory triplets.
- Analysis of multi-omics profiling data from The Cancer Genome Atlas (TCGA).
- Functional enrichment, transcriptional regulatory network, and protein-protein interaction (PPI) network analyses.
Main Results:
- Identification of 12,006 A-to-I RNA editing-mediated miRNA regulatory triplets across ten cancer types.
- Demonstration that these regulations impact key cancer-related functions including apoptosis, cell cycle, drug resistance, and immunity.
- Validation of triplets as potential biomarkers for cancer subtype classification and prediction of prognosis or drug response.
Conclusions:
- RNA editing-mediated miRNA regulation is a significant mechanism in cancer.
- These regulatory interactions play crucial roles in cancer progression and clinical outcomes.
- The developed resource (REMR) offers valuable insights into epitranscriptomic regulation in cancer.
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