Integrative analysis of significant RNA-binding proteins in colorectal cancer metastasis

J Cell Biochem. 2018 Dec;119(12):9730-9741. doi: 10.1002/jcb.27290. Epub 2018 Aug 21.

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.

Keywords: RNA-binding protein (RBP); colorectal cancer; machine learning; metastasis; survival analysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC-3G Deaminase / genetics
  • Algorithms
  • CELF Proteins / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Computational Biology / methods
  • DNA Copy Number Variations
  • Eukaryotic Initiation Factor-5 / genetics
  • Eukaryotic Translation Initiation Factor 5A
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Machine Learning
  • Peptide Elongation Factor 1 / genetics
  • Peptide Initiation Factors / genetics
  • RNA-Binding Proteins / genetics*

Substances

  • CELF Proteins
  • CELF3 protein, human
  • EEF1A2 protein, human
  • EIF5Al1 protein, human
  • Eukaryotic Initiation Factor-5
  • Peptide Elongation Factor 1
  • Peptide Initiation Factors
  • RNA-Binding Proteins
  • APOBEC-3G Deaminase
  • APOBEC3G protein, human