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Breast cancer is the most commonly diagnosed malignant tumor and the second-highest cause of cancer-related deaths in women worldwide. Circular RNAs (circRNAs) are associated with the development of numerous cancers, including breast cancer. Here, we present the first report that  circRPAP2  (hsa_circ_91) is downregulated in breast cancer tissue samples and cell lines. Furthermore, the expression level of  circRPAP2  in breast cancer tissues was correlated with axillary lymph node metastasis and TNM stage. Biological function studies demonstrated that  circRPAP2  inhibited the proliferation and migration of breast cancer in vivo and in vitro. The mechanistic evaluation indicated that  circRPAP2  can bind to the oncoprotein SRSF1, likely competing with the binding between SRSF1 and  PTK2  pre-mRNA, thereby attenuating SRSF1-mediated alternate splicing of PTK2, an effector of SRSF1 oncogenic activity, resulting in the reduction of PTK2 mRNA and protein expression. Overall, our findings suggest that  circRPAP2  plays a tumor suppressor role and may serve as a biomarker in breast cancer. In addition, the identification of the  circRPAP2 /SRSF1 / PTK2 axis provides new insights into the pathogenesis of breast cancer and highlights a novel target for the development of oncotherapeutics.

CircRPAP2 regulates the alternative splicing of PTK2 by binding to SRSF1 in breast cancer