# Dietary Soy Impact on Host Transcriptome Profile--A Review
## 4 Discussion
Moreover, the soy diet could counteract the age-related accumulation of iron stores, decreasing the risk for cardiovascular diseases [90]. An aspect that is often forgotten is that the soy diet has been shown to modulate the levels of specific mature microRNAs. Thus far, only two reports have assessed the relationship between soy intake and the changes in miRNA expression in mammals. [PERSON] et al. evaluated the association of long-term (one year), pre-diagnosis soy consumption with the expression of miRNAs in patients diagnosed with triple-negative breast cancer (TNBC) [47]. A long-term soy diet was associated with strong upregulation of 13 microRNAs, including the well-known tumor suppressor miR-29a-3p. [PERSON] et al. examined the liver of soy-fed male mice [46] and described the transcriptome impact of upregulated miR-145a-5p and miR-455-3p. Interestingly, the transcriptome analysis identified iron metabolism and xenobiotic/fatty acid metabolizing pathways as coordinately regulated by the two microRNAs. To the best of our knowledge, this is the first soy interventional study indicating that soy induced transcriptome changes might be due to post-transcriptional regulatory mechanisms. It is also worth noting that the conserved miR-150-5p was found to be upregulated in both studies, despite the differences in tissue analyzed (breast cancer cells vs. normal liver), duration of soy-diet (one year vs. one month), and species analyzed (humans vs. mice). This might suggest that miR-150-5p is part of mammals' common, evolutionary-conserved transcriptome response to soy-enriched diet. Of note, besides its role in lipid and iron metabolism, miR-150-5p is also known to be involved in carcinogenesis [91; 92]. Taken together, these findings indicate that the soy diet induces significant gene expression responses in different experimental models, an effect that could be modulated at both transcriptional and post-transcriptional levels. The best-known transcriptional factors mediating soy transcriptional effects are RICTOR (rapamycin-insensitive companion of TOR, complex 2) and SREBP1 (steroid regulatory element-binding transcription factor 1) [45; 46]. The soy-induced suppression of these two transcription factors protects against insulin resistance and fatty liver [93; 94]. CEBPD (CCAAT/ enhancer-binding protein delta), a transcriptional regulator that acts as a tumor suppressor, is strongly induced by soy-diet, which might explain the repression of multiple oncogene targets [39]. On the other hand, the impact on microRNA expression indicates that soy-induced gene regulation also involves post-transcriptional mechanisms [46; 47]. Significant data show that diet might lead to epigenetic changes such as DNA methylation or histone modifications [95]. Genistein has been shown to induce specific DNA methylation changes in rodents by altering coat color and protecting mice offspring from obesity [96]. Additionally, epigenetic changes associated with the soy diet were observed in primates [97; 98]. [PERSON] et al. described an interesting pattern of DNA methylation for seven primate genes, among which, unexpectedly, the homeobox genes. These changes were then related to lipid and glucose metabolism modifications, suggesting increased insulin sensitivity [97]. Moreover, epigenetic changes in Hox genes can affect a variety of cancers [99]. By analyzing the similarities and differences of soy-related transcriptome impact in several experimental models and tissues, this review is an attempt to better understand the gene expression changes induced by soy diet. Taken together, the transcriptome data analyzed here fully support the already known benefits/risks associated with the soybean diet. On the one hand, the common responses of fish and mammals (such as retinol, xenobiotic or ferprotosis pathways) under different experimental conditions point towards a possibly conserved transcriptome response to soy diet. On the other hand, we found some evident discrepancies between the two phyla regarding cholesterol and fatty acid pathways.