Analysis of Overexpressed miRNA in Circulation and Cancer Tissue to Develop a Potential microRNA Panel for the Diagnosis of Colorectal Cancer.

Background: Colorectal cancer (CRC) represents the world's fourth deadly cancer, but its early diagnosis can be curative with considerable success rates. This study was aimed to identify CRC-specific microRNAs (miRNAs) in tissue and serum samples to develop a miRNA-based diagnostics panel for the minimal invasive detection of CRC in early conditions.

Methods: By integrating four microarrays in tissue and serum samples of CRC from the Gene Expression Omnibus (GEO) database, we screened out the highly expressed miRNAs in each dataset using the limma R package. Two important upregulated miRNAs, namely hsa-miR-1246 and hsamiR- 1825, were overlapped in both tissue and serum samples of CRC and were investigated to target identification, followed by functional annotation and protein-protein interaction (PPI) study for the target genes through DAVID and STRING, respectively. Finally, hub target genes were retrieved by Cytoscape analysis.

Results: It was shown that target genes of hsa-miR-1246 and hsa-miR-1825 were involved with core KEGG pathways (such as cAMP, PI3K-Akt, and calcium signaling pathway). In addition, biological processes (such as cell adhesion and cell proliferation), cellular components (such as plasma membrane and cytosol), molecular functions (such as protein binding and metal ion binding) were mostly associated with the target genes. Their top 5 target genes were retrieved, and their biological function towards tumor progression was shown using Cancer Hallmarks Analytics Tool.

Conclusion: This study suggested that hsa-miR-1246 and hsa-miR-1825, as overlapped upregulated tissue and circulating miRNAs, might have a vital role in the development of CRC, and their five hub target genes were identified.