hsa-circKLK3-25 promotes epithelial-mesenchymal transition and malignant progression of prostate cancer through the JNK/ERK signaling pathway.

Prostate cancer (PCa) is one of the most common malignant tumors in males. Characterized by an insidious onset, the majority of patients are diagnosed at an advanced stage upon initial presentation. Therefore, it is particularly important to find the potential biomarkers for early diagnosis of PCa. The expression and stability of circKLK3-25 in PCa cells were assessed by qRT-PCR and Actinomycin D testing. Cell Counting Kit-8 assay, EdU staining, scratch-wound assay and transwell experiments were used to make clear the influences of circKLK3-25 on the progression of PCa cells. Target miRNAs of circKLK3-25 was analyzed by bioinformatics. Western blot determined the expressions of proteins associated with the JNK/ERK pathway and epithelial-mesenchymal transition (EMT). Finally, subcutaneous xenograft tumor models were formed in nude mice to uncover the interference of circKLK3-25 with PCa progression in vivo. The results showed that circKLK3-25 was significantly highly expressed in PCa cells with good stability. Overexpression circKLK3-25 propelled PCa cells to proliferate, invade, migrate, and EMT process; conversely, silencing circKLK3-25 impaired the malignant biological properties of such cells. Overexpression circKLK3-25 led to upregulation of JNK/ERK signaling pathway-related proteins, while silencing circKLK3-25 lead to the opposite trend. Pathway inhibitors attenuated the pro-oncogenic effects of overexpression of circKLK3-25. circKLK3-25 was a sponge for miR-874-3p, and overexpression of miR-874-3p suppressed the PCa malignant phenotype and EMT. Besides, in vivo experiments demonstrated that overexpression circKLK3-25 activated the JNK/ERK signaling pathway and promoted tumor growth, and silencing circKLK3-25 did the opposite. In conclusion, circKLK3-25 is notably overexpressed in PCa cells and promotes PCa malignant progression through activating JNK/ERK signal pathway.