Discov Oncol. 2025 Dec 11. doi: 10.1007/s12672-025-04257-6. Online ahead of print.
ABSTRACT
ORC1 is a core protein governing DNA replication initiation and cell cycle regulation, exhibiting significant overexpression in multiple malignancies where it correlates with advanced disease stage and poor prognosis. It drives tumor progression through diverse mechanisms including activation of ERK/JNK and Wnt signaling pathways, inhibition of ferroptosis via SLC7A11, and promotion of epithelial-mesenchymal transition. Its expression is regulated through multiple layers including m6A modification by IGF2BP1, the XIST/miR-140-5p axis, transcription factors like ETV4, and epigenetic regulators including EZH2. ORC1 represents a promising therapeutic target, as its inhibition induces replication stress, cell cycle arrest, and enhances sensitivity to existing chemotherapeutic agents. Future research should focus on developing specific ORC1 inhibitors and exploring their synergistic potential with immunotherapy and targeted therapies.
PMID:41379386 | DOI:10.1007/s12672-025-04257-6