Histone deacetylase inhibitors (HDACi) induce miR-125a-5p to inhibit tumorigenesis. R2N1d-YFP and R2N1d-GFP-mir-125a-5p cells were injected into the right flank of immunodeficient mice (n = 6 per group), and 1 week later, Trichostatin A (TSA) (500 μg/kg body weight) or normal saline was injected into the tumor once every 2 days for 30 days. (a) Tumor images were captured by in vivo imaging and (b) photon flux was measured with the AxioVision Software. (c) Tumor thin sections were analyzed with fluorescence microscopy, hematoxylin and eosin (H&E) staining, TUNEL, in situ hybridization with miR-125a-5p and immunohistochemistry with anti-HDAC5. (d) A model is reported in which TSA determine RUNX3/p300 complex to the miR-125a-5p promoter through acetylating of RUNX3 and accordingly miR-125a-5p upregulation, gives rise to HDAC5 downregulation and subsequent apoptosis activation.