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

ABSTRACT

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.