Exosomes from CD133 ⁺ cells carrying circ‐ABCC1 mediate cell stemness and metastasis in colorectal cancer

Abstract

Colorectal cancer (CRC), a fatal tumor, has been diagnosed as one of the most prevalent types of cancers globally, inducing multiple cancer-linked deaths. Mounting evidence has revealed that circular RNA (circRNA) elicits a regulatory impact on the initiation and development of cancers. Emerged as a new circRNA, hsa_circ_0000677 (circ-ABCC1) has not been studied in cancer progression. This study is the first attempt to explore the regulatory role of circ-ABCC1 in CRC. In this study, data from sphere-forming, transwell, and Western blot analyses revealed that cell stemness, sphere formation, and metastasis were notably enhanced in CD133⁺ cells isolated from CRC cells. In addition, exosomes from CD133⁺ cells could promote cell stemness, sphere formation, and metastasis. Moreover, circ-ABCC1 was verified to be characterized with a loop structure through quantitative reverse-transcription polymerase chain reaction analysis. Functional assays testified that the upregulation of circ-ABCC1 contributed to cell stemness, sphere formation, and metastasis in CD133^- /Caco2 or CD133^- /HCT15 cells. Furthermore, the interaction between circ-ABCC1 and β-catenin was analyzed via RNA immunoprecipitation and RNA pull-down and finally, circ-ABCC1 was confirmed to facilitate CRC progression by activating the Wnt/β-catenin pathway. To sum up, exosomes from CD133⁺ cells carrying circ-ABCC1 can mediate cell stemness and metastasis in CRC, unveiling that circ-ABCC1 serves as a novel candidate target for CRC treatment.