MiR‐99a exerts anti‐metastasis through inhibiting myotubularin‐related protein 3 expression in oral cancer

<jats:sec><jats:title>Objective</jats:title><jats:p>We aimed at studying the role of the most deregulated miR‐99a, identifying its downstream targets, and exploring the clinical potential of miR‐99a and its target(s) in oral cancer.</jats:p></jats:sec><jats:sec><jats:title>Subjects and Methods</jats:title><jats:p>Following confirmation of miR‐99a deregulation in nine oral lines and 26 pairwise clinical specimens, miR‐99a‐manipulated oral cancer cells were subjected to cell proliferation, migration, invasion, and in vivo murine metastasis assays. We characterized putative miR‐99a target(s) using luciferase reporter assays and genetic manipulation. The inverse relation of miR‐99a and its target(s) was examined in clinical specimens using real‐time <jats:styled-content style="fixed-case">PCR</jats:styled-content> and Western blot analysis.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>MiR‐99a down‐regulation was confirmed both in tested oral cancer cell lines and clinical specimens. Ectopic miR‐99a expression inhibited oral cancer cell migration and invasion. Anti‐miR‐99a, silencing miR‐99a functions, had the opposite effect. Myotubularin‐related protein 3 (<jats:styled-content style="fixed-case">MTMR</jats:styled-content>3) with one evolutionarily conserved seed region in the 3′‐untranslated region was a novel miR‐99a target. Depleting <jats:styled-content style="fixed-case">MTMR</jats:styled-content>3 expression significantly reduced cell proliferation, migration, or invasion. There was an inverse expression of miR‐99a and <jats:styled-content style="fixed-case">MTMR</jats:styled-content>3 protein in oral cancer lines and clinical specimens.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>miR‐99a repressed oral cancer cell migration and invasion partly through decreasing <jats:styled-content style="fixed-case">MTMR</jats:styled-content>3 expression. <jats:styled-content style="fixed-case">MTMR</jats:styled-content>3 may serve as a therapeutic target for oral cancer treatment.</jats:p></jats:sec>