Identification of an MiRNA-mRNA Regulatory Network in Colorectal Cancer

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Author(s): Ming-fu Cui, Yuan-yu Wu, Ming-yan Chen, Yang Zhao, Song-yun Han, Rui-jie Wang, Haiyan Zhang, Xue-dong Fang*

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

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Background: Colorectal cancer (CRC) is the fourth most prevalent cancer in the world. However, the molecular mechanism underlying CRC is largely unknown.

Objective: To explore the pathogenic mechanism of CRC and to facilitate better diagnosis and treatment of this disease.

Methods: Differentially expressed miRNAs (DEMs) and genes (DEGs) in CRC vs. Control samples from the miRNA expression data in GSE115513 and the miRNA and mRNA expression data in TCGA-COAD dataset were screened, followed by the construction of miRNA-mRNA regulatory network. Functional and pathway enrichment analysis, protein-protein interaction (PPI) analysis, and survival analysis were then performed for these DEGs and DEMs.

Results: We identified 64 DEMs from GSE115513 dataset and 265 DEMs and 2218 DEGs from TCGA-COAD dataset. miR-27a-3p was a hub DEM with the highest degree in miRNA-mRNA network, while GRIN2B and PCDH10 were hub DEGs targeted by multiple miRNAs, including miR-27a-3p. SNAP25 and GRIN2B were also hub DEGs with the highest degree of interactions in PPI network. These DEMs and DEGs were significantly enriched in multiple KEGG pathways, including proteoglycans expression and cAMP signaling pathway in cancer. Finally, seven DEGs, including FJX1 Dsc2, and hsa-miR-375, were revealed to be correlated with CRC prognosis.

Conclusions: Aberrant expression of genes and miRNAs were involved in the pathogenesis of CRC probably by regulating proteoglycans expression and cAMP signaling. miR-27a-3p, PCDH10, GRIN2B, FJX1, Dsc2, and hsa-miR-375 were identified as potential targets for understanding the pathogenic mechanism of CRC. In addition, FJX1, Dsc2 and hsa-miR-375 were identified as potential predictive markers for CRC prognosis.

Keywords: Colorectal cancer, TCGA-COAD, miRNA-mRNA regulatory network, microRNA, survival analysis, biomarker.

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(E-pub Ahead of Print)
DOI: 10.2174/1386207323666201110154142
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