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Background: This study aimed to investigate interactions between miR-214, PTEN, and WWOX and their effect on AKT signaling during the NPC progression. Nasopharyngeal carcinoma (NPC) was highly prevalent with poor prognosis among the patients. MiR-214 reported as an important NPC biomarker was associated with regulation of biological functions. Methods: 5-8F and 6-10B NPC cells were transfected with miR-214 inhibitor. MTT and colony formation assays were performed to assess cell proliferation. PI staining assay was performed to determine distribution of cell cycle. Annexin-V/PI staining assay was used to evaluate cell apoptosis in NPC. The effects of miR-214 inhibitor on the expression levels of PTEN, WWOX, AKT signaling pathway, cell-cycle-, and apoptosis-associated proteins were assessed by Western blotting or qRT-PCR assay. PTEN and WWOX were knocked down using the corresponding shRNA to investigate their effects on miR-214 inhibitor involved in proapoptosis and antiproliferation mechanisms in NPC. Results: Inhibition of miR-214 suppressed cell growth and induced apoptosis of 5-8F and 6-10B cells. MiR-214 regulated the expression of both PTEN and WWOX through targeting the 3'-UTR. Inhibition of miR-214 promoted WWOX and PTEN expression, inactivated AKT signaling pathway, and regulated cell-cycle- and apoptosis-associated proteins. Knockdown of PTEN or WWOX reversed effects of miR-214 inhibitor on AKT signaling, cell proliferation, and apoptosis. Conclusion: MiR-214 was suggested to induce cell proliferation and inhibit cell apoptosis of NPC through directly targeting both PTEN and WWOX, which provided a novel therapeutic target for clinical treatment of NPC. [ABSTRACT FROM AUTHOR]