A CS•CBE System Targeting β-Catenin: Exploring Additional Inhibition Targets for Colon Cancer Proliferation

Abstract

Colon cancer ranks among the most prevalent malignant tumors worldwide, with its incidence rising progressively year by year. The identification of novel research tool for therapeutic targets has thus become an urgent priority. Here, we constructed a CS•CBE integrative delivery and editing system via chitosan and cytosine base editor (CBE), which could successfully target and inhibit the phosphorylation of β-catenin. In vitro studies demonstrated that this system achieved a high delivery efficiency of 86.0% and an editing efficiency of 78% in HCT116 cells, and Transwell and wound-healing assays verified that the CBE-β-catenin-HCT116 cells exhibited an increased proliferation rate. Furthermore, a xenograft tumor model was established in nude mice, and we observed that the tumor volume and weight in the experimental group were both significantly increased compared with those in the control group. Subsequently, the candidate genes identified from transcriptomic results, such as AXIN2 and GPR15, which are downstream of β-catenin pathways, validated the feasibility of the CS•CBE system as a research tool. Collectively, our CS•CBE system serves as a valuable research tool for targeted protein modulation, downstream target identification, and probe specific post-translational modifications analysis in colon cancer research.