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Our data further uncovered that circ-ITCH could bind directly to miR-421 and block its repression on PDCD4 in OSCC. MiR-421 expression was significantly increased in OSCC tissues and was inversely correlated with circ-ITCH expression. Notably, miR-421 restoration blocked the tumor-suppressive role of circ-ITCH in OSCC cells. In conclusion, our study reveals that circ-ITCH serves as a tumor suppressor in OSCC partly by regulating miR-421/PDCD4 axis. In conclusion, our study reveals that circ-ITCH serves as a tumor suppressor in OSCC partly