The Potential Role of Egg‐Derived Xeno‐ <scp>miRs</scp> in Chemotherapy Response: An In Silico Approach

Exogenous microRNAs (Xeno-miRs), primarily derived from dietary sources, are detectable in host biofluids and influence gene expression through cross-kingdom regulation. Despite growing interest, their impact on human diseases, especially cancer, remains controversial and requires further investigation. However, the specific implications of diet-derived Xeno-miRs in chemotherapy response remain largely unexplored. This study assesses the potential functions and possible implications of egg-derived miRNAs in chemotherapy response with an in silico approach. This study presents the first evaluation of the contribution of diet-derived miRNAs in modulating chemotherapy outcomes. Egg-derived miRNAs were retrieved from the Dietary MicroRNA Database, and their human homologs were identified. Target genes and transcription factors were predicted using mirDIP and TransmiR databases, respectively. Pathway enrichment analysis was conducted with DIANA-miRPath. Expression patterns of Xeno-miRs were analyzed using the CancerMIRNome database, and differentially expressed target genes were identified using TCGA and GTEx data via GEPIA2. The chemotherapy response of Xeno-miRs was assessed using ncRNADrug. Fifty-five egg-derived Xeno-miRs were initially retrieved, among which 17 human homologs were further analyzed. Notably, the downregulation of <i>hsa-miR-30a-5p</i> and <i>hsa-miR-146a-5p</i> was associated with increased sensitivity to fluorouracil and oxaliplatin, whereas the overexpression of <i>hsa-miR-22-3p</i> and <i>hsa-miR-200a-3p</i> was linked to resistance against testosterone and bortezomib (<i>p</i> < 0.0001, logFC ≥ 2 or ≤ -2). This study provides in silico evidence for the role of dietary miRNAs in chemotherapy response, paving the way for their translational application in nutrition-based cancer management strategies. Further experimental studies are required to quantify their bioavailability post-digestion and to characterize their cellular uptake mechanisms.