CircSKA3 in Colorectal Cancer: Molecular Mechanisms, Therapeutic Potential, and Translational Challenges

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and is the second leading cause of cancer death globally. The current treatment of CRC encompasses surgical resection, chemotherapy, targeted therapy, and immunotherapy and the two main problems that need to be addressed are drug resistance and metastatic recurrence. Circular RNAs (circRNAs) is a newly discovered class of covalently closed non-coding RNAs that have been found to play important roles in regulation of gene expression and tumor biology in recent years. One of them, circSKA3 (hsa_circ_0000467), has been shown in pre-clinical studies to have oncogenic potential in CRC and multiple other cancers. CircSKA3 executes its mechanism through activating multiple pathways to promote tumor cell invasion, metastasis, and epithelial-mesenchymal transition (EMT). Clinical studies have shown that inhibiting circSKA3 with antisense oligonucleotides (ASOs), small interfering RNA (siRNA) and CRISPR-Cas13 systems completely reduces tumor growth. Therefore, circSKA3 association has high potential translational value despite some limitations of technical achievement such as efficient delivery, off-target effects, and corroboration with large clinical cohorts. This article provides a systematic overview of the molecular mechanisms of circSKA3, considers its role and potential as a biomarker and therapeutic target, and reviews the possibilities and challenges of developing circSKA3-based intervention strategies for the treatment of CRC.