# Dietary Soy Impact on Host Transcriptome Profile--A Review
## 4 Discussion
Closely related to cholesterol metabolism, steroid hormone biosynthesis is another pathway common to fish and mammals. Rodent _Cyp4A14_, a member of the cytochrome P450 monooxygenases family, considered female-predominant [71], was overexpressed in the liver. Moreover, genes such as _Hsh17b_ (hydroxysteroid 17-beta dehydrogenase family), involved in androgen and estrogen metabolism [72], were deregulated. In mammals, _Hsh17b6_ (essential for dihydrotestosterone-DHT-biosynthesis and involved in the pathophysiology of Polycystic Ovary Syndrome) [73] was downregulated. In fish, _hsh17b7_, involved in the activation of estrogens (estrone to estradiol) and inactivation of androgens (dihydrotestosterone to androstanediol), was overexpressed [73]. Estradiol stimulates breast carcinogenesis while dihydrotestosterone (DHT) inhibits it [74]. Hence, the anti-carcinogenic effect of the soy diet might be explained by the modulation of _17f-HSD_ (17f-hydroxysteroid dehydrogenase) gene activity in breast cancer cells through its phytoestrogenic effects, presumably mediated by [PERSON]'s high affinity for the estrogen receptor [75; 76]. Another expected fish-mammal common pathway targeted by the soy diet is retinol metabolism. Retinoids are obtained solely from the diet (and soybeans are rich in vitamin A), being required for maintaining normal growth, development, reproduction, vision, and a healthy immune system [77]. The clinical use of retinoids is known to induce hypertriglyceridemia [78], a side effect that could be counteracted by soy protein diet supplementation since soy is known to inhibit signaling through RAR-beta (Retinoic acid receptor beta) in the liver [78; 79]. One should add that in the analysis of the fish dataset, we noticed a downregulation of _retsat_ (retinoid saturase). _Retsat_ has an important role in adipogenesis (promotes normal differentiation) and is downregulated in obese mice and humans [80]. Both phyla showed a downregulation of several UGT (UDP-Glucuronosyltransferases) superfamily genes. Based on current knowledge, xenobiotic metabolism (common among mammals and fish) is one of the main pathways altered by the soy diet [81]. UGT enzymes are essential members of phase I and II drug metabolism, which convert endogenous and exogenous lipophilic metabolites into more polar, less toxic, and easy to excrete compounds. They are often considered modulators for xenobiotics and steroids, thereby controlling their potency and availability [82]. We noticed downregulation of various genes from UGT1 and UGT2 families; since phytestrogens' most important detoxification pathway is glucuronidation, this effect (most probably mediated by genistein) explains the pro-estrogenic role of soy diet supplementation [71]. Soy-induced diet inhibition of UDP-glucuronosyltransferases genes might increase the toxicity of anti-cancer drugs and contribute to drug resistance of cancer cells [83; 84; 85]. One of the fish-mammal common pathways, found enriched after STRING analysis of the pooled datasets (Method 2) is ferptosis. Ferroptosis is a unique iron/ROS-dependent form of cell death driven by the accumulation of iron-dependent lipid peroxidation products [86]. Fe\({}^{3+}\) is imported into the cell through TFR (transferrin receptor) and then reduced to Fe\({}^{2+}\), released in the cytoplasm by SLC11A2 (Solute Carrier Family 11 Member 2) metal transporter [87]. Ferroptosis is a natural tumor suppressor pathway and plays a significant anti-cancer role [88]. In our study, multiple inhibitors of ferptosis, such as _Slc7a11_ (Solute Carrier Family 7 Member 11), _Alox15_ (15-lipoxygenase), and _Ftl_ (Ferritin Light Chain) were found downregulated. Recent studies demonstrated that the overexpression of _Slc7a11_ promotes tumor growth by suppressing ferprotosis [89]. By increasing iron uptake and reducing iron storage, the soy diet might promote ferprotosis; this could explain the reports linking soy diet to anti-tumoral effect and provides yet another strategy for cancer therapy.