One fundamental issue in public health is the safety of food products derived from plants and animals. A recent study raised a concern that microRNAs, which widely exist in everyday foods, may alter consumers’ functions. However, some studies have strongly questioned the likelihood of dietary uptake of functional microRNAs in mammals. Here we use a microRNA gene knockout animal model to show that miR-144/451 null mice can orally uptake miR-451 from a daily chow diet, and ingestion of wild type blood, that contains abundant miR-451, also enhances the level of miR-451 in the circulating blood of knockout mice. Moreover, reducing miR-451 level in miR-144/451 knockout blood by consuming food lacking miR-451 reduces the anti-oxidant capacity of miR-144/451 null red blood cells by targeting the 14-3-3ζ/Foxo3 pathway, while increasing miR-451 level via gavage-feeding of wild type blood increases the anti-oxidant capacity of miR-144/451 null red blood cells. We conclude that 1) some miRNAs in food can pass through the gastrointestinal tract into the blood to affect consumers’ function and 2) microRNA knockout animals such as miR-144/451 null mice can acquire the deleted genetic information from daily foods, which might alter the results and conclusions from the studies using such animals.

Background: Circular ribonucleic acids (circRNAs) are highly stable and conserved forms of RNAs present in all eukaryotes. They can modulate the expression of genes by sponging specific micro RNAs (miRNAs), thereby affecting various disease processes. However, their expression pattern in human breast cancer has not been elucidated.Methods: In this study, differentially expressed circRNAs in breast cancer tissues and paired noncancerous tissues were analyzed using an Arraystar Human circRNA Microarray, and hsa_circ_0006220 was selected for its 27-fold downregulation in breast cancer tissues. Its expression was also verified in 50 breast cancer and paired noncancerous tissues using real-time polymerase chain reaction (RT-PCR). An analysis of the expression of hsa_circ_0006220 and the clinicopathological factors in breast cancer was conducted. A receiver operating characteristic (ROC) curve of hsa_circ_0006220 was constructed. The interaction between hsa_circ_0006220 and five possible target miRNAs was predicted, and their expression were verified when overexpressing hsa_circ_0006220 by RT-PCR.Results: Hsa_circ_0006220 was found to be significantly downregulated in breast cancer tissues compared to the paired noncancerous tissues by microarray and RT-PCR. The expression of hsa_circ_0006220 was significantly inversely correlated with histological type (P=0.0028) and lymph node metastasis (P=0.0341).The area under the ROC curve (AUC) was 0.706. Five miRNAs that might be sponged by hsa_circ_0006220 were predicted. MiR-197-5p was significantly downregulated after overexpression of hsa_circ_0006220. Conclusions:Our results indicated that hsa_circ_0006220 may play a role in human breast cancer and might be a potential tumor marker for breast cancer screening.