Targeting the MCM10/p53/p21/CCND1 Axis in Colorectal Cancer: Evaluating the Therapeutic Potential of Ultrasound

Background: Colorectal Cancer (CRC), the second leading cause of cancer-related deaths globally, continues to lack effective early diagnostic biomarkers and therapeutic strategies. Minichromosome maintenance protein 10 (MCM10), a replication initiation factor implicated as a pan-cancer marker, remains poorly characterized in CRC. Its role within the p53/p21/Cyclin D1 (CCND1) regulatory axis and its potential as a therapeutic target, particularly under ultrasound-based modulation, warrants investigation. Methods: Integrated bioinformatic analyses were conducted using public databases to evaluate MCM10 expression and clinical significance. Clinical CRC specimens were analyzed via qPCR and immunohistochemistry to validate MCM10 expression. Functional assays, including colony formation, cell counting kit-8 (CCK-8), Transwell migration/invasion, and flow cytometry, assessed the biological effects of MCM10 knockdown on proliferation, Apoptosis, and cell cycle. Western blotting and rescue experiments elucidated signaling pathways. A CRC mouse xenograft model was established to evaluate in vivo tumor growth. The therapeutic modulation of MCM10-related pathways using ultrasound-based interventions was preliminarily assessed. Results: MCM10 expression was significantly upregulated in cell lines and CRC tissues, and correlated with poor prognosis. Silencing MCM10-impaired CRC cell proliferation, invasion, migration, and induced G1/S cell cycle arrest suppressed epithelial-mesenchymal transition and increased Apoptosis. Mechanistically, MCM10 knockdown activated the p53/p21 axis and downregulated CCND1 expression. In vivo, MCM10 inhibition suppressed xenograft tumor growth. Ultrasound exposure exhibited the potential to enhance the therapeutic effects of MCM10 suppression by modulating the MCM10/p53/p21/CCND1 axis. Conclusions: These findings reveal that MCM10 promotes CRC malignancy through inhibiting the tumor-suppressive p53/p21/CCND1 pathway. Targeting this axis, particularly through ultrasound-enhanced delivery or sensitization strategies, holds promise as a novel therapeutic approach in CRC.

CCND1; MCM10; colorectal cancer; p21; p53.