Abstract

ObjectiveThe aim of the study was to find the key genes, microRNAs (miRNAs) and transcription factors (TFs) and construct miRNA-target gene-TF regulatory networks to investigate the underlying molecular mechanism in colorectal adenoma (CRA).MethodsFour mRNA expression datasets and one miRNA expression dataset were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were identified between CRA and normal samples. Moreover, functional enrichment analysis for DEGs was carried out utilizing the Cytoscape-plugin, known as ClueGO. These DEGs were mapped to STRING database to construct a protein-protein interaction (PPI) network. Then, a miRNA-target gene regulatory network was established to screen key DEMs. In addition, similar workflow of the analyses were also performed comparing the CRC samples with CRA ones to screen key DEMs. Finally, miRNA-target gene-TF regulatory networks were constructed for these key DEMs using iRegulon plug-in in Cytoscape.ResultsWe identified 514 DEGs and 167 DEMs in CRA samples compared to healthy samples. Functional enrichment analysis revealed that these DEGs were significantly enriched in several terms and pathways, such as regulation of cell migration and bile secretion pathway. A PPI network was constructed including 325 nodes as well as 890 edges. A total of 59 DEGs and 65 DEMs were identified in CRC samples compared to CRA ones. In addition, Two key DEMs in CRA samples compared to healthy samples were identified, such as hsa-miR-34a and hsa-miR-96. One key DEM, hsa-miR-29c, which was identified when we compared the differentially expressed molecules found in the comparison CRA versus normal samples to the ones obtained in the comparison CRC versus CRA, was also identified in CRC samples compared to CRA ones. The miRNA-target gene-TF regulatory networks for these key miRNAs included two TFs, one TF and five TFs, respectively.ConclusionThese identified key genes, miRNA, TFs and miRNA-target gene-TF regulatory networks associated with CRA, to a certain degree, may provide some hints to enable us to better understand the underlying pathogenesis of CRA.

Highlights

  • MATERIALS AND METHODSColorectal adenoma (CRA) is defined as non-cancerous lesion of the large intestinal epithelium

  • We compared the differentially expressed molecules found in the comparison CRA versus normal samples to the ones obtained in the comparison colorectal cancer (CRC) versus CRA

  • A total of 80 overlaps were screened among these differentially expressed genes (DEGs) and target genes of differentially expressed miRNAs (DEMs)

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Summary

Introduction

MATERIALS AND METHODSColorectal adenoma (CRA) is defined as non-cancerous lesion of the large intestinal epithelium. It is commonly acknowledged that CRA is a precancerous condition and may progress to colorectal cancer (CRC) that is a common reason of cancer death worldwide, with the unknown etiology and pathogenesis (Fearon, 2010; Kim et al, 2020). A recent study demonstrated that 5 miRNA ratios were significantly up-regulated in serum samples from patients with CRC compared with the ones from patients with CRA (Zhang et al, 2018). Notwithstanding studies of differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) have been carried out in the last few years and some of their biological function have been elucidated, the detailed mechanisms associated with the pathogenesis of CRA still remain poorly understood on account of a limited number of identified genetic alterations and unknown interactions among DEGs and DEMs

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