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For the in vitro characterization, HIPK2 was depleted in human CRC cells by CRISPR/Cas9 or RNA interference. HIPK2‑proficient and HIPK2‑defective cells were evaluated for their response to 5‑fluorouracil (5‑FU) and oxaliplatin (OXA). The results revealed that HIPK2 depletion induced resistance to 5‑FU and OXA, and that this resistance was not overcome by brusatol, an inhibitor of the antioxidant response regulator nuclear factor erythroid 2‑related factor 2 (NRF2), which is frequently overexpressed in CRC. By contrast, cell sensitivi