Butyrate may reduce CRC risk through decreasing the effect of exposure to carcinogens from foods. discussed. Furthermore, evidence on the effect of butyrate on CRC risk through reducing oncogenic miRNA expression will be presented. and spp and the type and ratio of microbiota in the gut can influence the amount of butyrate produced.25,29 In addition to the microbiota, dietary intake can influence the production of butyrate. For example, cellulose, lignin, and some insoluble fibre have Adarotene (ST1926) low ferment ability, so the production of butyrate from these sources is usually low.30 Besides dietary fibre, other butyrate Adarotene (ST1926) substrates, such as the oligosaccharides acarbose and tributyrin, can increase butyrate production in the colon.31 Butyrate regulates inflammation, immunity, and oxidative balance and can function as histone deacetylase inhibitors (HDACi) to promote human health.15 In addition, butyrate is an important energy source (providing 5%-15% of caloric requirements30) and controls cell proliferation, differentiation, and apoptosis in colon cells (Physique 1).15,32,33 Open in a separate Adarotene (ST1926) window Determine 1. The effects of butyrate on colon cells. HDAC indicates histone deacetylase. In both in vivo and in vitro studies, it has been reported that butyrate has bioactivity to reduce colon cancer risk.22 Butyrate can modulate immune response in the colon and regulate the balance of gut bacteria to maintain colon homeostasis and reduce colon carcinogens (Physique 1).34 In this way, butyrate can ameliorate the CRC risk induced by high consumption of red and processed meat, although there is some conflicting data in this regard.22,30,34,35 HDACI are used as chromatin-modifying drugs to treat cancers and other diseases.36 Butyrate has the ability to inhibit HDAC activity and thus inhibit DNA damage and the activation of oncogenes.36C38 Table 1 shows a summary of effects of butyrate on colon and other cancer types. Table 1. Anti-cancer properties of butyrate through regulating miRNA and gene expression. and P53Suppressor 59 MiR-21Initiation and progressionand P53Promoter64,66MiR-145ProgressionInsulin receptor substrate 1 and insulinlike growth factor receptor 1Controversial 59 MiR-17-19 clusterProgression and MACC1Suppressor71,72 Open in a separate window In CRC, miRNAs are involved in initiation, progression, and metastasis. There are several miRNAs commonly associated with colon cancers, such as Let-7, miR-21, miR-145, miR-17-19 cluster, miR-221, and miR-143, among others21,59,64 (Table 2). Moreover, Chiang et al65 claimed that miR-192, miR-194, and miR-215 are associated with increased tumour size in colon cancer. It is essential to understand the role of miRNA expression in colon cancer to create effective preventive and therapeutic methods. MicroRNA expression can be modulated by dietary nutrients.58,60 Generally, vitamins, minerals, and bioactive components in foods are considered to maintain peoples health and protect against some diseases. The effect of nutrients on regulating miRNA expression may help explain how these nutrients affect health. Hu et al73 reported that butyrate can modulate miRNA expression in colon cancer such that the expressions of Let-7, miR-17-92a, miR-18-106a, and miR-25-106b clusters are decreased. Effects of Butyrate on miRNA Expression in CRC Cells In CRC cells, miRNA expression is largely associated with cancer initiation, progression, and metastasis. MicroRNA expression can be modulated by dietary factors including butyrate, and thus butyrate, as well as other dietary bioactives, could be used to create a less carcinogenic environment. is an important signalling pathway in CRC initiation which regulates both cell proliferation and colonic cell differentiation. This pathway can be regulated by SCFAs.74 In addition, Lazarova et al75 investigated the effect of butyrate around the Wnt signalling pathway which Adarotene (ST1926) is associated with the induction of apoptosis. They found that Wnt signallingCspecific gene expression was modified by butyrate in the CRC HCT-116 cell line.75 In turn, miRNAs can regulate the expression Mmp7 of the genes involved.75 Therefore, there may be some association between butyrate and miRNA expression in CRC initiation. In a.