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

Abstract

Abstract 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_0000091) 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.