Bladder cancer is one of the most frequently occurring malignant tumors in the urinary system. Sodium butyrate (NaB) is a histone deacetylase inhibitor and exerts remarkable antitumor effects in various cancer cells. MicroRNAs (miRNAs) and autophagy play crucial roles in cancer occurrence and development. In the present study, we evaluated the anticancer effects, including cell migration inhibition and the apoptotic effects of NaB in human bladder cancer cells. Furthermore, we found that NaB inhibited migration and induced AMPK/mTOR pathway‐activated autophagy and reactive oxygen species (ROS) overproduction via the miR‐139‐5p/Bmi‐1 axis. In addition, we found that ROS overproduction contributed to NaB‐induced caspase‐dependent apoptosis and autophagy. The interplay between autophagy and apoptosis in NaB treatment was clarified. Our findings provide a further understanding of EMT reversion, apoptosis and autophagy induced by antitumor drugs and a novel perspective and alternative strategy for bladder cancer chemotherapy.

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Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal uroepithelial cells, circRIMS1 was selected as a research object. We further verified by qRT-PCR that circRIMS1 is upregulated in both bladder cancer tissue and cell lines. Proliferation, colony-formation, Transwell migration, invasion, apoptosis, western blotting, and in vivo experiments were utilized to clarify the roles of circRIMS1, microRNA (miR)-433-3p, and cell cycle and apoptosis regulator 1 (CCAR1). For mechanistic investigation, RNA pulldown, fluorescence in situ hybridization (FISH), and luciferase reporter assay confirmed the binding of circRIMS1 with miR-433-3p. Inhibition of circRIMS1 suppressed the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo . Moreover, the circRIMS1/miR-433-3p/CCAR1 regulatory axis was confirmed to be responsible for the biological functions of circRIMS1. Taken together, our research demonstrated that circRIMS1 promotes tumor growth, migration, and invasion through the miR-433-3p/CCAR1 regulatory axis, representing a potential therapeutic target and biomarker in bladder cancer.