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Rosmarinic acid inhibits migration, invasion, and p38/AP-1 signaling via miR-1225-5p in colorectal cancer cells

Abstract Elucidating the molecular mechanism of the migration and invasion is critical for identifying novel therapeutic targets and may significantly improve the prognosis of colorectal cancer. Emerging evidence suggests an involvement of dysregulated microRNAs in the process of tumorigenesis. Here, we show that miR-1225-5p prevents migration and invasion of colorectal cancer cells. Overexpression of miR-1225-5p significantly decreases the expression of Matrix Metalloproteases (MMPs)-1, 3, and 9. Knockdown of miR-1225-5p elevates ROS level via regulating Keap1/Nrf2 pathway. Furthermore, miR-1225-5p attenuates IL-17A-induced p38/AP-1-signaling pathway by suppressing IL-17RA expression. We also examined the biological effects of Rosmarinic acid (RA) on metastatic colorectal cancer cells. RA inhibited EMT via the p38/AP-1 signaling, and miR-1225-5p is essential for RA-mediated anti-metastatic effects.