Tumor cell exosome circ-0023919 promotes EMT through the miR-197-5p/ICAM5 axis and enhances the drug resistance of colorectal cancer to 5-fu.

5-Fluorouracil (5-Fu) is a cornerstone chemotherapeutic agent in the treatment of colorectal cancer (CRC). However, its clinical efficacy is frequently hampered by the development of drug resistance, which remains a major obstacle to successful treatment. The aim of this study is to gain a comprehensive understanding of the role and mechanism of the tumor cell-derived exosomal circ-0023919 in 5-Fu resistance. High-throughput microarray technology was employed to identify differentially expressed circRNAs in 5-Fu resistance CRC cells and their derived exosomes. A CRC/5-Fu drug-resistant cell line was successfully established using the drug gradient induction method, and its resistance index was subsequently determined. We employed transmission electron microscopy, nanoparticle tracking analysis (NTA) and Western blot to characterize exosomes by detecting the exosomal markers CD63 and TSG101. The circular structure, stability, and subcellular localization of circ-0023919 were confirmed using a combination of approaches, including actinomycin D treatment, RNase R digestion, specific primer PCR amplification, Sanger sequencing and FISH. Furthermore, we systematically evaluated the regulatory role of circ-0023919 in multiple biological functions of CRC cells by assessing cell proliferation, migration, invasion, drug resistance, stemness and EMT-related markers. Our findings demonstrate that circ-0023919 promotes the migration and invasion of CRC/5-Fu cells both in vitro and in vivo, while also enhancing resistance to 5-Fu chemotherapy. Mechanistically, circ-0023919 acts as a molecular sponge for miR-197-5p, thereby upregulating the expression of ICAM5. In this scientific study, circ-0023919 is shown to enhance the resistance of CRC cells to 5-Fu by promoting EMT. Thus, circ-0023919 is considered a potential therapeutic target for CRC treatment.