Ultrasound-targeted microbubble destruction mediated upregulation of CNN1 induces ferroptosis in colorectal cancer cells by regulating p53-related SLC7A11 expression.

Colorectal cancer (CRC) represents a leading cause of cancer-related mortality, with patients often demonstrating suboptimal responses to current therapeutic modalities, underscoring the need for innovative treatment therapies. Ultrasound-targeted microbubble destruction (UTMD) has emerged as a promising technique to enhance gene transfection efficiency. While previous research has established the critical role of CyclinD1 (CNN1) in the pathogenesis of multiple cancer types, its involvement in CRC progression remains underinvestigated. In this study, we sought to elucidate the impact of UTMD-mediated CNN1 modulation on CRC progression. In the present study, data indicate that CNN1 is underexpressed in CRC and may contribute to CRC progression. UTMD-assisted transfection of CNN1 exhibits significantly higher efficiency compared to liposomes (LIP)-mediated transfection. UTMD-mediated CNN1 overexpression potently inhibits CRC cell proliferation and promotes cell apoptosis. Mechanistic investigations reveal that UTMD-drivenCNN1 overexpression suppresses CRC cell proliferation via the p53 signaling pathway. Further studies confirm that SLC7A11 is overexpressed in CRC tissues, whereas CNN1 overexpression downregulates SLC7A11 expression. Notably, p53 inhibits SLC7A11 transcription by directly binding to its promoter region. Rescue experiments demonstrate that UTMD-mediated CNN1 overexpression induces ferroptosis through activation of the p53-SLC7A11 pathway. Collectively, UTMD-driven upregulation of CNN1 elicits ferroptosis in CRC cells by modulating p53-associated SLC7A11 expression. These findings highlight CNN1 as a potential target for therapeutic intervention and diagnostic strategies in CRC.