Extracellular vesicle‐derived circ_SLC19A1 promotes prostate cancer cell growth and invasion through the miR‐497/septin 2 pathway

Abstract The occurrence and development of prostate cancer (PCa) is complex, and the related mechanism is not fully understood. Current studies have found that extracellular vesicles (EVs) and circular RNAs (circRNAs) have important functions in various tumours and other diseases. In this study, the detection of circRNAs in PCa showed that circ_SLC19A1 was increased in PCa cells and their secreted EVs. EVs with high expression of circ_SLC19A1 could be taken up by PCa cells, which promoted cell proliferation and invasion. The sequence of circ_SLC19A1 contained multiple binding sites for miR‐497, and circ_SLC19A1 could bind directly to miR‐497 in cells. The expression of miR‐497 was downregulated in PCa cells, while the expression of its target gene septin 2 (SEPT2) was upregulated significantly. Transfection of circ_SLC19A1 small interfering RNA (siRNA) or miR‐497 mimics could significantly inhibit the expression of SEPT2 and the phosphorylation of extracellular signal‐regulated kinase 1 and 2 (ERK1/2). After co‐transfection of circ_SLC19A1 siRNA and miR‐497 inhibitors or SEPT2 overexpression vector, the expression of SEPT2 and ERK1/2 phosphorylation levels showed no significant changes. Similar results were obtained with co‐transfection of miR‐497 mimics and the SEPT2 overexpression vector. Therefore, cancer cells can regulate the expression of SEPT2 through miR‐497 by secreting EVs with high expression of circ_SLC19A1, thus affecting the activation of the downstream ERK1/2 pathway and ultimately regulating PCa cell growth and invasion. Therefore, EV‐derived circ_SLC19A1 plays an important regulatory role in PCa and may be an important target for PCa prevention and treatment.