Breast cancer currently represents the most prevalent cancer globally, with metastasis being the primary cause of mortality among breast cancer patients. The research team led by Prof. Zu Xuyu from the First Affiliated Hospital of University of South China has long been committed to the research on the pathogenesis, prevention,treatment of breast cancer. On September 16, 2023, Prof. Zu Xuyu published a research paper titled “Downregulated circPOKE promotes breast cancer metastasis through activation USP10-Snail axis” in the renowned international oncology journal, Oncogene. The latest research findings elucidate the tumor-suppressive role of the Pokemon-derived circular RNA—circPOKE. This is achieved by competitively binding to the deubiquitinase USP10, thereby promoting the ubiquitination degradation of Snailinhibiting breast cancer invasionmetastasis.

Through RT-PCRFISH analyses of patient samples (adjacent/normal tissues, primary/metastatic breast cancer tissues), the study revealed that circPOKE expression was downregulated in tumor tissuesfurther reduced in metastatic breast cancer. Overexpression of circPOKE significantly suppressed metastasis potential of breast cancer cells both in vitroin vivo. Further research demonstrated that both circPOKESnail directly interact with USP10, a member of the deubiquitinating enzymes (DUBs) family, exhibiting a competitive binding relationship. This competitive binding inhibited the interaction between USP10SNAIL, thus promoting the protein ubiquitinationdegradation of Snail,ultimately inhibiting the epithelial-mesenchymal transition (EMT)metastasis of breast cancer cells. In addition, this study also found that circPOKE is enriched within exosomes secreted by breast cancer cells. CircPOKE-loaded exosomes markedly inhibited lung metastasis in tumor-bearing mice. This work provides novel therapeutic strategiesexperimental evidence for breast cancer treatment, which has important clinicalscientific significance.

Professor Zu Xuyu’s team has long focused on mechanisms underlying breast cancer stemnessmetastasis. In recent years, the team has published multiple research papers in prestigious international journals including Nature Communications, Oncogene, Cell Death & Disease,International Journal of Cancer. The first author of this publication is Luo Yan, a master’s student in the class of 2020, with Professor Zu XuyuAssociate Professor Feng Jianbo serving as corresponding authors. This research was funded by the National Natural Science Foundation of China, the Natural Science Foundation of Hunan Province,the “4310” Research Plan of Clinical Medicine Research of University of South China.