Freeze-dried black raspberry (BRB) powder is considered as a potential cancer chemopreventive agent. In this study, we fed azoxymethane (AOM)/dextran sodium sulfate (DSS)-treated C57BL/6J mice with a diet containing BRB anthocyanins for 12 weeks, and this led to a reduction in colon carcinogenesis. These animals had consistently lower tumor multiplicity compared with AOM/DSS-treated mice not receiving BRB anthocyanins. In AOM/DSS-treated mice, the number of pathogenic bacteria, including Desulfovibrio sp. and Enterococcus spp., was increased significantly, whereas probiotics such as Eubacterium rectale, Faecalibacterium prausnitzii and Lactobacillus were dramatically decreased, but BRB anthocyanins supplement could reverse this imbalance in gut microbiota. BRB anthocyanins also caused the demethylation of the SFRP2 gene promoter, resulting in increased expression of SFRP2, both at the mRNA and protein levels. Furthermore, the expression levels of DNMT31 and DNMT3B, as well as of p-STAT3 were downregulated by BRB anthocyanins in these animals. Taken together, these results suggested that BRB anthocyanins could modulate the composition of gut commensal microbiota, and changes in inflammation and the methylation status of the SFRP2 gene may play a central role in the chemoprevention of CRC.

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As important epigenetic regulators, microRNA regulate protein expression by triggering the degradation of target mRNA and/or by inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including colorectal cancer. In this study, microRNA-array differential analysis revealed strongly enhanced expression of miR-24-1-5p in the colon tissue of azoxymethane/dextran sulphate sodium-induced mice that were fed with black raspberry anthocyanins for 9 weeks. Overexpression of miR-24-1-5p in human colorectal cancer cells significantly repressed β-catenin expression, and simultaneously decreased cell proliferation, migration and survival. Furthermore, miR-24-1-5p could target β-catenin and trigger a negative regulatory loop for β-catenin and its downstream target genes. β-Catenin signalling is vital to the formation and progression of human colorectal cancer. The current findings therefore identified miR-24-1-5p as a potent regulator of β-catenin, and this may provide a novel chemopreventive and therapeutic strategy for β-catenin signalling-driven colorectal cancer.