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MiR‐376c Inhibits Metastasis by Controlling RUNX2‐INHBA Axis in Oral Squamous Cell Carcinoma

Aberrant microRNA expression is a common phenotype in cancer cell progression. MicroRNA is the negative regulator of hundred to thousand gene expressions. Here we report chr14q32.2 miRNA cluster significantly down‐regulated in clinical OSCC samples. 19 miRNAs were found with coordinated silencing in OSCC patients. However, their specific target and regulation mechanism have not clearly identified. Here we showed miR‐376c is the most significant microRNA down‐regulated by RT‐Q‐PCR validation in the miRNA cluster. Ectopic expression of miR‐376c not only inhibited oral cancer cells proliferation, but also migration and invasion. MiR‐376c also inhibited the in vivo tumorigenesis and metastasis. Furthermore, miR‐376c was found directly binding to the 3′‐UTR of oncogenic transcription factor, RUNX2, which was found significantly up‐regulated in OSCC patients. Silencing of RUNX2 inhibited OSCC proliferation and invasion through INHBA expression. Taken together, our study demonstrates the tumor suppressor role of miR‐376c, which regulates RUNX2 transcriptomes in OSCC. Moreover, our results indicate RUNX2‐INHBA axis may play important roles in OSCC progression.