Prostate cancer (PCa) is the second frequent malignancy among men in the world. Exosomal circular RNAs(circRNAs) have been reported to function in PCa progression. The current study aimed to investigate the roleof exosomal circRNA homeodomain-interacting protein kinase 3 (circHIPK3) in PCa development. Exosomeswere extracted from serum and cells utilizing commercial kit, and identified by transmission electron microscopy(TEM), Western blot assay and nanoparticle tracking analyzer. Relative expression of circHIPK3,microRNA (miR)-212 and B-cell specific MMLV insertion site-1 (BMI-1) was examined by quantitative realtimePCR or Western blot assay. Receiver Operating Characteristic (ROC) analysis was conducted to assess thediagnostic potential of exosomal miR-212. Cell viability, and metastasis including migration and invasion,were detected by Methyl thiazolyl tetrazolium (MTT) assay and Transwell assay, respectively. Cell apoptosiswas monitored using flow cytometry. The interaction between miR-212 and circHIPK3 or BMI-1 was validatedby dual-luciferase reporter assay. Xenograft tumor assay was employed to explore the role of exosomalcircHIPK3 in vivo. Exosomal circHIPK3 was increased in serum of PCa patients, and could discriminate PCapatients from normal volunteers. Depletion of exosomal circHIPK3 or overexpression of exosomal miR-212reduced viability, migration and invasion, but promoted cell apoptosis in PCa cells, which was attenuated bymiR-212 inhibition or BMI-1, respectively. MiR-212 targeted BMI-1, and downregulated BMI-1 expression.Exosomal circHIPK3 knockdown also suppressed tumor growth in vivo. Exosomal circHIPK3 knockdowninhibited PCa progression by regulating miR-212/BMI-1 axis, at least in part, offering a new insight into themolecular mechanism of PCa.
Volume 47, 2022
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