Inhibition of Circ_0081234 Reduces Prostate Cancer Tumor Growth and Metastasis Via the MiR-1/MAP 3 K1 Axis

Introduction: Circular RNAs (circRNAs) are crucial regulators of tumor occurrence and progression, and circRNAs are enriched and stable in exosomes. The present study aimed to explore the role and potential mechanism of cancer-derived exosomal circ_0081234 in prostate cancer (PCa).

Methods: Exosomes were extracted using the ExoQuick Precipitation Kit (System Biosciences, Mountain View, CA, USA). The levels of circ_0081234, miR-1 and mitogen-activated protein kinase kinase kinase 1 (MAP 3 K1) were examined using a quantitative real-time polymerase chain reaction or western blotting. Cell migration and invasion were evaluated via a transwell assay. The protein levels of N-cadherin, vimentin and E-cadherin were detected by western blotting. The interaction between miR-1 and circ_0081234 or MAP 3 K1 was verified via a dual-luciferase reporter assay and an RNA pull-down assay.

Results: The circ_0081234 level was increased in PCa tissues with spinal metastasis in comparison to primary PCa tissues without spinal metastasis. Exosomal circ_0081234 promoted the migration, invasion and epithelial-mesenchymal transition of PCa cells. Knockdown of circ_0081234 blocked PCa cell progression by regulating miR-1. In addition, miR-1 overexpression suppressed PCa cell progression by repressing MAP 3 K1. Moreover, circ_0081234 increased MAP 3 K1 level via sponging miR-1. Depletion of circ_0081234 inhibited tumor growth in vivo.

Conclusions: Exosomal circ_0081234 promoted migration, invasion and epithelial-mesenchymal transition of PCa cells by regulating the miR-1/MAP 3 K1 axis.