Specific Regulatory Motifs Network in SARS-CoV-2-Infected Caco-2 Cell Line, as a Model of Gastrointestinal Infections.

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was primarily noted as a respiratory pathogen, but later clinical reports highlighted its extrapulmonary effects particularly on the gastrointestinal (GI) tract. The aim of the current study was the prediction of crucial genes associated with the regulatory network motifs, probably responsible for the SARS-CoV-2 effects on the GI tract. The data were obtained from a published study on the effect of SARS-CoV-2 on the Caco-2 (colon carcinoma) cell line. We used transcription factors-microRNA-gene interaction databases to find the key regulatory molecules, then analyzed the data using the FANMOD software for detection of the crucial regulatory motifs. Cytoscape software was then used to construct and analyze the regulatory network of these motifs and identify their crucial genes. Finally, GEPIA2 (Gene Expression Profiling Interactive Analysis 2) and UALCAN datasets were used to evaluate the possible relationship between crucial genes and colon cancer development. Using bioinformatics tools, we demonstrated one 3edge feed-forward loop motifs and recognized 10 crucial genes in relationship with Caco-2 cell infected by SARS-CoV-2, including SP1, TSC22D2, POU2F1, REST, NFIC, CHD7, E2F1, CEBPA, TCF7L2, and TSC22D1. The box plot analysis indicated the significant overexpression of CEBPA in colon cancer compared to normal colon tissues, while it was in contrast with the results of stage plot. However, the overall survival analysis indicated that high expression of CEBPA has positive effect on colon cancer patient survivability, verifying the results of CEBPA stage plot. We predict that the SARS-CoV-2 GI infections may cause a serious risk in colon cancer patients. However, further experimental studies are required.