Author ORCID Identifier
Date of Award
Doctor of Philosophy (PhD)
IEC-specific overexpression of CD98 mediates intestinal inflammation and intestinal epithelial barrier dysfunction in experimental colitis and increase the susceptibility to colitis-asociated cancer. Here we demonstrated homeostatic gene profile dysregulation in the villus-crypt axis via CD98 overexpression. Using miRNA-target gene prediction module, we observed differentially expressed miRNAs to target proteins of villus and crypt profoundly affected by CD98 overexpression. We have utilized online bioinformatics as methods to further scrutinize the biological meanings of miRNA-target data. We identified significant interactions among the differentially regulated proteins targeted by altered miRNAs in Tg mice. The biological processes affected by the predicted targets of miRNAs deviate from the homeostatic functions of the miRNA-gene-protein axis of the wildtype mice. Our results emphasize a dynamic perturbation of miRNA and protein expression in villus-crypt axis contributing to potential biological consequences of altering CD98 expression. Such mechanism of endogenous miRNA gene-protein network dysregulation via host gene modification as modeled in our animal study has great implication in the translational understanding of the etiology of inflammatory bowel disease (IBD) in human population. It is hypothesized that diet-derived miRNAs, or exogenous miRNAs, can also potentially modify host gene expression profile. Various miRNAs have been detected in both plant and animial-derived foods. Furthermore, diet has been implicated as a potential facilitator of microbiota activities in gut health. We found evidence of consumption of foods typically known as junk food in US adult population with IBD. The idea that miRNAs from the exogenous source such as food can be another co-factor as a potential underlying mechanism behind the differential effect of food and diet on IBD risk and pathogenesis is quite feasible. The concept adds another layer of complexity in the interplay between the host, genetics, immune system, microbiota, and food and environment in the pathogenesis of IBD.
Han, Moon, "The Role of CD98 in Dysregulation of MiRNA and Protein Expression Along the Villus-Crypt Axis in Intestinal Epithelium." Dissertation, Georgia State University, 2019.
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