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Characterizing the tumor RBP-ncRNA circuits by integrating transcriptomics, interactomics and clinical data
Leiming Jiang1, Qiuyang Chen1, Mingrong Bei1
1Computational Systems Biology Laboratory, Department of Bioinformatics, Shantou University Medical College (SUMC), 515041 Shantou, China.
Abstract:
The interactions among non-coding RNA (ncRNA) and RNA binding protein (RBP) are increasingly recognized as one of basic mechanisms in gene regulation, and play a crucial role in cancer progressions. However, the current understanding of this regulation network, especially its dynamic spectrum according to the differentially expressed nodes (i.e. ncRNAs and RBP) is limited. Utilizing transcriptomics and interactomics resources, dysregulated RBP-ncRNA circuits (RNCs) are systematically dissected across 14 tumor types. We found these aberrant RNCs are robust and enriched with cancer-associated ncRNAs, RBPs and drug targets. Notably, the nodes in altered RNCs can jointly predict the clinical outcome while the individual node can't, underscoring RNCs can serve as prognostic biomarkers. We identified 30 pan-cancer RNCs dysregulated at least in six tumor types. Pan-cancer RNC analysis can reveal novel mechanism of action (MOA) and repurpose for existing drugs. Importantly, our experiments elucidated the novel role of hsa-miR-224-5p, a member of the pan-cancer RNC hsa-miR-224-5p_MAGI2-AS3_MBNL2, in EMT program. Our analysis highlights the potential utilities of RNCs in elucidating ncRNA function in cancer, associating with clinical outcomes and discovering novel drug targets or MOA.
Insights
Dysregulated RNA binding protein-non-coding RNA circuits (RNCs) are key in cancer progression. These RNCs can predict patient outcomes and reveal new drug targets, offering insights into cancer mechanisms.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Non-coding RNA (ncRNA) and RNA binding protein (RBP) interactions are fundamental to gene regulation and cancer progression.
- Understanding the dynamic regulatory network of ncRNA-RBP interactions, particularly in cancer, remains limited.
Purpose of the Study:
- To systematically dissect dysregulated RNA binding protein-non-coding RNA circuits (RNCs) across various cancer types.
- To investigate the potential of RNCs as prognostic biomarkers and therapeutic targets in cancer.
Main Methods:
- Utilized transcriptomics and interactomics data to identify and analyze aberrant RNCs in 14 tumor types.
- Performed pan-cancer analysis to identify common dysregulated RNCs across multiple cancers.
- Conducted experimental validation to elucidate the role of a specific RNC in cancer progression.
Main Results:
- Identified robust, dysregulated RNCs enriched with cancer-associated genes and drug targets.
- Demonstrated that altered RNCs, but not individual nodes, can jointly predict clinical outcomes, serving as prognostic biomarkers.
- Discovered 30 pan-cancer RNCs and elucidated the role of the hsa-miR-224-5p_MAGI2-AS3_MBNL2 circuit in epithelial-mesenchymal transition (EMT).
Conclusions:
- Dysregulated RNCs are significant in cancer, offering potential as prognostic biomarkers and for drug repurposing.
- Pan-cancer RNC analysis provides novel insights into cancer mechanisms and therapeutic strategies.
- The study highlights the utility of RNCs in understanding ncRNA function, clinical outcomes, and drug discovery in oncology.
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