The Translational Impact of Plant-Derived Xeno-miRNA miR-168 in Gastrointestinal Cancers and Preneoplastic Conditions.

INTRODUCTION: Diet is one of the most important factors contributing to the multistep process of carcinogenesis. The clinical relevance of exogenous food-derived xeno-microRNAs (miRNAs) in human diseases is poorly understood. In this study, we aimed to evaluate the potential clinical relevance of the xeno-miRNA miR-168 in the gastric mucosa along the preneoplastic conditions and gastric carcinogenesis. METHODS: For a systematic analysis, we included stomach tissues from patients with different pathologies, including normal mucosa (N), chronic non-atrophic (CNAG) and atrophic gastritis (CAG) and intestinal metaplasia (IM) (n = 72), matched non-tumorous (NT) and tumorous (T) gastric cancer (GC) tissues (n = 81), matched colorectal cancer (CRC) tissues (n = 40), and colon mucosa and faeces from controls and IBD patients. RESULTS: miR-168 was reproducibly detectable in all samples studied, with the highest levels in the proximal upper GI and in non-tumorous compared to tumorous tissues in both GC and CRC. There was no difference related to H. pylori positivity or inflammation grade, while higher miR-168 levels were observed in patients with moderate or severe AG/IM or OLGIM3/4. Survival analysis showed only a small, non-significant trend towards worse overall survival for patients with the highest to lowest miR-168 levels, while no differences were related to Lauren's classification. CONCLUSIONS: Food-derived xeno miRNAs are reproducibly detectable in the gastric and colonic mucosa. Although the clinically relevant function remains to be elucidated, higher levels of miR-168 in patients with moderate and severe IM merit further investigation.

Food-Derived Xeno-microRNAs: Influence of Diet and Detectability in Gastrointestinal Tract-Proof-of-Principle Study.

SCOPE: Diet is amongst the most crucial factors contributing to the multistep process of carcinogenesis. The role of exogenous microRNAs (miRNAs) is still debatable. In this proof-of-principle work, the presence of miRNAs in a variety of foods, its stability to processing, and detectability in GI mucosa and feces are studied and the effect of short-term diet on human- or plant-derived miRNAs in feces and blood is examined. METHODS AND RESULTS: Animal and plant miRNAs are detected in all foods irrespective of processing. Animal-derived foods showed the highest miRNA level and the lowest is found in cheese and milk. The impact of the short-term vegetarian or meat-rich diet on blood and feces miRNA is evaluated in healthy subjects using qPCR and Affymetrix profiling. Diet is not associated with changes in ultraconserved miRNAs. However, a vegetarian diet is associated with an increase of miR-168 in feces but not in blood. Overall, plant miR-168 is detectable in normal GI mucosa and in colorectal cancer. CONCLUSIONS: Food provides a great source of miRNAs and diet may be associated with changes in xenomiRs. Plant-derived miR-168 is ubiquitously present in feces, normal mucosa, and cancer. Further studies are needed to evaluate the functional interaction between diet-derived miRNAs and GI tract.