Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA interaction network regulating intestinal...

Area of Science:

• Molecular Biology
• Bioinformatics
• Systems Biology

Background:

• Intestinal epithelial barrier function is crucial for homeostasis and is regulated by complex molecular networks.
• Dysregulation of this barrier is linked to inflammation, osmotic issues, and cancer development.
• MicroRNA-mRNA interactions are key regulators but are challenging to predict and validate.

Purpose of the Study:

• To develop a computational method for identifying hypothetical mRNA-miRNA interaction networks.
• To analyze these networks in the context of intestinal epithelial barrier regulation.
• To identify specific genes and microRNAs involved in cellular proliferation and cancer.

Main Methods:

• Utilized functional-molecular databases (KEGG, miRWalk2.0) to generate mRNA-miRNA interaction lists.
• Developed a network modeling approach using R-code for data analysis and visualization.
• Integrated RNA expression data from Nanostring nCounter® system with network analysis.

Main Results:

• A novel network model was created to identify co-regulatory motifs in mRNA-miRNA interactions.
• A specific sub-network was identified, highlighting shared targeting microRNAs.
• Key genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D, were pinpointed within this network.

Conclusions:

• The developed network model effectively identifies hypothetical mRNA-miRNA interactions regulating epithelial function.
• This approach aids in understanding the complexity of competing-endogenous RNA networks.
• The findings highlight potential therapeutic targets within cancer-related gene networks.