MicroRNA-433 Inhibits Migration and Proliferation of Nasopharyngeal Carcinoma by Targeting Hypoxia- Induced Factor 1α

Abstract Background Nasopharyngeal carcinoma (NPC) is a malignancy of head and neck cancer. miR-433 was downregulated in various of cancers. However, the roles and underlying mechanisms of miR-433 in the hypoxic microenvironment of NPC have not been clarified. Methods Real-time quantitative PCR, Western blot assay were performed to examine miR-433 and hypoxia-inducible factor-1α (HIF-1α) levels in NPC tissue and cells. Cell proliferation, migration of differentially expressed miR-433 cells was measured by Cell Counting Kit-8, Transwell analysis in vitro. Nude mice and zebrafish model were used to confirm the effect of miR-433 in vivo. Luciferase reporter assays was used to determine whether HIF-1α was a direct target of miR-433. Results RT-qPCR, Western blot assay were performed to show that miR-433 was down-regulated while hypoxia-inducible factor-1α (HIF-1α) was overexpressed in NPC. Cell proliferation, migration of differentially expressed miR-433 cells was measured by CCK8, Transwell analysis in vitro. Our data showed that miR-433 suppressed proliferation and migration of hypoxic NPC cells by directly binding the 3'-untranslated region (UTR) of HIF-1α. Knockdown the expression of HIF-1α in the miR-433 inhibitor treated hypoxic CNE2 cells partially reversed the effect. Nude mice and zebrafish model were used to confirm the effect of miR-433 in vivo. Luciferase reporter assays was used to determine whether HIF-1α was a direct target of miR-433. Conclusions NPC cells proliferation, migration, cell cycle arrest, colony formation, and the epithelial mesenchymal transition (EMT) progression were all inhibited by miR-433 by directly targeting HIF-1α. miR-433 could act as cancer suppressor miRNA and represent an effective therapeutic strategy for NPC.