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The therapeutic effect of combined miR-375 + 5-FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR-375-3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5-FU. © 2020 The Authors. Cancer Science published by John Wiley Sons Australia, Ltd on behalf of Japanese Cancer Association.Immunotherapy has become a hotspot in cancer therapy in recent years. Several immune checkpoints inhibitors ha