Amcinonide Exhibits Antitumor Effects in Radioresistant Colorectal Cancer Through the circRNF10/miR‐296‐5p/Snail Axis

Radiotherapy, commonly used in the treatment of colorectal cancer (CRC), can induce local recurrence and malignant progression in cases of intrinsic and acquired radioresistance; therefore, effective treatment strategies are required. In this study, we screened an FDA-approved drug library and identified amcinonide (AMC), a topical corticosteroid, as a potential agent that inhibits radiation-induced epithelial-mesenchymal transition (EMT), cell migratory ability, and invasiveness in radioresistant colorectal cancer cells. Mechanistically, ionizing radiation-induced circRNF10 suppressed miR-296-5p, thereby increasing Snail expression and promoting EMT and aggressive phenotypes in radioresistant CRC cells. We verified in vitro, in vivo, and in CRC patient-derived organoids (PDOs) models that AMC suppresses the malignant phenotype by restoring miR-296-5p expression and reducing Snail expression. These findings identify the circRNF10/miR-296-5p/Snail axis as a key factor in CRC radioresistance and suggest that it may serve as a therapeutic target. Together, these results suggest that AMC is a promising drug for overcoming CRC radioresistance and that components of this axis may serve as potential diagnostic biomarkers. Overall, these findings highlight the therapeutic potential of targeting the ncRNA-mediated EMT circuit to overcome radioresistant CRC.