miR-433 inhibits oral squamous cell carcinoma (OSCC) cell growth and metastasis by targeting HDAC6

• miR-433 is downregulated in OSCCs and it can inhibit OSCC cell growth, invasion and migration.
• miR-433 directly targets HDAC6.
• Overexpression of HDAC6 can rescue miR-433 induced OSCC cells growth inhibition.
• Overexpression of HDAC6 can rescue miR-433 induced OSCC cells invasion and migration inhibition.

SummaryObjectivesThe aim of this study was to determine expression levels of miR-433 in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues, and explore its biological functions in OSCCs.MethodsmiR-433 level in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues was tested by real-time qPCR. The effect of miR-433 on cell growth was detected by MTT and colony formation assays. The tumorigenicity of miR-433 transfected OSCCs was evaluated in nude mice model. Transwell and wound healing assays were performed to detect the effect of miR-433 on OSCCs cell invasion and migration. Luciferase reporter gene assays were performed to identify the interaction between miR-433 and 3′UTR of HDAC6 mRNA. The protein level of HDAC6, BCL2, CCNE1, MMP1 and MMP9 was determined by Western blotting. Immunohistochemistry analysis was performed to detect the expression of HDAC6 in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues.ResultsWe found that miR-433 was frequently down-regulated in OSCCs compared with adjacent normal tissues. Restoring miR-433 expression in OSCC cells dramatically suppressed cells growth, invasion and migration. Importantly, our data showed that miR-433 downregulated the expression of HDAC6 through directly targeting its 3′UTR.ConclusionOur data suggest that miR-433 exerts its tumor suppressor function by targeting HDAC6, leading to the inhibition of OSCC cell growth, invasion and migration, which suggest that miR-433 may be potential target for diagnostic and therapeutic applications in OSCC.