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Accumulating evidence demonstrates that microRNAs (miRNAs or miRs) play important roles in the development and progression of human malignancies, including oral squamous cell carcinoma (OSCC); however, the unique roles of miRNAs are not yet fully understood in OSCC. The present study aimed to identify novel miRNAs associated with OSCC and to elucidate their functions. Based on a microarray analysis, miR‑144‑3p was found to be one of the most significantly downregulated miRNAs in OSCC tissues. Its low expression was closely associated with tumor size, differentiation and lymph node metastasis. Functionally, miR‑144‑3p overexpression suppressed proliferation, promoted apoptosis, and suppressed the invasion and migration of OSCC cells. In addition, enhancer of zeste homolog 2 (EZH2), a well‑known oncogene, was proven to be a direct target of miR‑144‑3p, and its protein expression was negatively regulated by miR‑144‑3p. Moreover, EZH2 expression was increased, and inversely correlated with the miR‑144‑3p level in OSCC tissues. Notably, EZH2 knockdown inhibited cell proliferation, promoted cell apoptosis, and suppressed the invasion and migration of OSCC cells, whereas EZH2 overexpression partially reversed the anticancer effects mediated by miR‑144‑3p overexpression. On the whole, the findings of the present study suggest that miR‑144‑3p functions as a tumor suppressor by targeting the EZH2 oncogene, and may thus be considered as a potential diagnostic and therapeutic target for OSCC.

miR‑144‑3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the downregulation of the oncogenic gene, EZH2