AM22 Inhibites the Proliferation of Colorectal Cancer by Targeting CBFB

Our previous studies have revealed the important roles of the non-seed regions of miRNAs in gene regulation, which provided a novel insight in the development of miRNA analogs for cancer therapy. Here, we altered each nucleotide in the non-seed region of miR-34a and obtained novel synthetic miRNA analogs. Among them, AM22 with a base alteration from G to C at the 17th nucleotide of miR-34a, showed extensive anti-proliferative activity against several colorectal tumor cell lines, and achieved effective inhibition of CBFB (core binding factor subunit β) expression. Subsequent investigations demonstrated that AM22 directly targeted CBFB by binding to its 3'-untranslated region (3'-UTR). Inhibition of CBFB showed obvious anti-proliferative activity on HCT-116 and SW620 cells. Furthermore, the anti-proliferative effects of AM22 on these cells were also measured in the xenograft mouse models. In conclusion, this study identified AM22 as a potential anti-tumor miRNA by targeting CBFB, and provided a new design approach for miRNA-based cancer treatment by changing the non-seed region of miRNA.