Notably, USP38 plays a crucial role in amplifying oxaliplatin and 5-Fu resistance by removing Lysine 63 ubiquitin chains from histone deacetylase 3 (HDAC3) in CRC cells, accompanied by an increase in H3K27 acetylation [76] (Fig. 2B). Here, HDAC3 is linked to colorectal carcinoma.