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MiR‐99a exerts anti‐metastasis through inhibiting myotubularin‐related protein 3 expression in oral cancer
Author(s) -
Kuo YZ,
Tai YH,
Lo HI,
Chen YL,
Cheng HC,
Fang WY,
Lin SH,
Yang CL,
Tsai ST,
Wu LW
Publication year - 2014
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12133
Subject(s) - cancer , metastasis , microrna , ectopic expression , biology , cancer cell , western blot , gene silencing , cancer research , cancer cell lines , cell culture , medicine , gene , genetics
Objective 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. Subjects and Methods 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 PCR and Western blot analysis. Results 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 ( MTMR 3) with one evolutionarily conserved seed region in the 3′‐untranslated region was a novel miR‐99a target. Depleting MTMR 3 expression significantly reduced cell proliferation, migration, or invasion. There was an inverse expression of miR‐99a and MTMR 3 protein in oral cancer lines and clinical specimens. Conclusion miR‐99a repressed oral cancer cell migration and invasion partly through decreasing MTMR 3 expression. MTMR 3 may serve as a therapeutic target for oral cancer treatment.