Identification of an MiRNA-mRNA Regulatory Network in Colorectal Cancer

Area of Science:

• Genomics
• Molecular Biology
• Cancer Research

Background:

• Colorectal cancer (CRC) is a major global health concern, ranking as the fourth most common cancer worldwide.
• The intricate molecular mechanisms driving CRC development and progression remain largely unelucidated, hindering effective diagnosis and treatment strategies.

Purpose of the Study:

• To elucidate the molecular pathogenesis of colorectal cancer.
• To identify potential biomarkers for improved diagnosis and therapeutic targeting of CRC.

Main Methods:

• Screening of differentially expressed microRNAs (DEMs) and genes (DEGs) in CRC versus control samples using TCGA-COAD and GSE115513 datasets.
• Construction of a miRNA-mRNA regulatory network, followed by functional enrichment, pathway analysis, and protein-protein interaction (PPI) network analysis.
• Survival analysis was conducted to identify genes and miRNAs correlated with CRC prognosis.

Main Results:

• Identification of 64 DEMs in GSE115513 and 265 DEMs and 2218 DEGs in TCGA-COAD.
• miR-27a-3p emerged as a key regulatory miRNA, targeting hub genes GRIN2B and PCDH10. GRIN2B and SNAP25 were identified as significant nodes in the PPI network.
• Enrichment analysis revealed involvement in pathways such as proteoglycans expression and cAMP signaling. Seven DEGs, including FJX1 and Dsc2, and hsa-miR-375 showed correlation with CRC prognosis.

Conclusions:

• Aberrant gene and miRNA expression, particularly involving proteoglycans and cAMP signaling, contributes to CRC pathogenesis.
• miR-27a-3p, PCDH10, GRIN2B, FJX1, Dsc2, and hsa-miR-375 are proposed as potential targets for understanding CRC mechanisms.
• FJX1, Dsc2, and hsa-miR-375 demonstrate potential as predictive biomarkers for colorectal cancer patient outcomes.