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Integrative analysis of significant RNA-binding proteins in colorectal cancer metastasis
Abstract:
The aberrant expression of RNA-binding proteins (RBPs) plays a crucial role in the occurrence and progression of human cancer. However, the key functions of RBPs in the metastasis of colorectal cancer have not yet been fully elucidated. Here, we integrated multi-omics data and identified four differentially expressed RBPs (APOBEC3G, EEF1A2, EIF5AL1 and CELF3) in patients with colorectal cancer metastasis. To clarify the underlying molecular mechanisms, we systematically analyzed the genomic features and downstream regulatory relationships of the four RBPs. In a genomic level, the copy number variations of APOBEC3G, EEF1A2, and CELF3 demonstrated significantly differential distributions between metastatic and nonmetastatic patients. Besides that, combining sequence and expression information, we identified 436 putative RNA targets regulated by the four RBPs through strict multistep bioinformatics screening. For the downstream analysis, the evidence from functional enrichment analysis and public literature indicated the roles of these target genes in the carcinogenesis and progression of colorectal cancer. Furthermore, through the machine learning algorithm and statistical analysis, we obtained two gene candidates that had obvious effects on the metastasis and overall survival status of patients with colorectal cancer. In summary, our study comprehensively explored the influence of APOBEC3G, EEF1A2, EIF5AL1, and CELF3 in colorectal cancer metastasis, which may offer favorable perspectives for clinical diagnosis and therapy.
Insights
Aberrant RNA-binding proteins (RBPs) drive colorectal cancer metastasis. This study identifies four key RBPs and their targets, revealing mechanisms and potential therapeutic strategies for metastatic colorectal cancer.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Aberrant expression of RNA-binding proteins (RBPs) is implicated in human cancer development and progression.
- The specific roles of RBPs in colorectal cancer (CRC) metastasis remain incompletely understood.
Purpose of the Study:
- To identify key RBPs involved in colorectal cancer metastasis.
- To elucidate the molecular mechanisms and downstream targets of these RBPs in CRC metastasis.
- To identify potential biomarkers for CRC metastasis and patient survival.
Main Methods:
- Integrated multi-omics data analysis to identify differentially expressed RBPs in metastatic CRC.
- Genomic analysis of copy number variations for identified RBPs.
- Bioinformatic screening to identify putative RNA targets of the RBPs.
- Functional enrichment analysis and machine learning for downstream target gene evaluation.
Main Results:
- Identified four differentially expressed RBPs (APOBEC3G, EEF1A2, EIF5AL1, CELF3) in metastatic CRC patients.
- Found significant copy number variations in APOBEC3G, EEF1A2, and CELF3 between metastatic and non-metastatic patients.
- Identified 436 putative RNA targets regulated by these four RBPs, implicated in CRC carcinogenesis and progression.
- Discovered two gene candidates significantly impacting CRC metastasis and overall survival.
Conclusions:
- APOBEC3G, EEF1A2, EIF5AL1, and CELF3 play significant roles in colorectal cancer metastasis.
- The identified RBPs and their targets offer potential avenues for clinical diagnosis and therapeutic intervention in metastatic CRC.
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