The aim of the present study was to investigate the roles of microRNA (miR)‑138 and interferon‑stimulated gene 15 (ISG15) in patients with oral squamous cell carcinoma (OSCC). miR‑138 and ISG15 expression in cancer tissues was detected, and the influence on proliferation, migration and invasion of OSCC cell lines was assessed. Reverse transcription‑quantitative polymerase chain reaction was performed to analyze the expression of miR‑138 and ISG15 in resected cancer tissues and pericancerous tissues harvested from patients with OSCC. The protein level of ISG15 was determined via western blot analysis. The constructed pGCMV/EGFP/miR‑138 plasmid was transfected into CAL27 and SCC‑15 OSCC cell lines via a liposome method to upregulate miR‑138 expression. The transfection efficiency was determined based on miR‑138 expression levels, and changes in proliferation, migration and invasion were subsequently compared with those in untransfected cells. The expression of ISG15 mRNA and protein was also detected in OSCC cells. miR‑138 was significantly downregulated (P<0.05) in cancer tissues compared with adjacent normal tissues in patients with OSCC, whereas ISG15 mRNA expression levels were significantly higher in pericancerous tissues (P<0.05). ISG15 protein levels were also significantly higher in pericancerous tissues (P<0.05). ISG15 protein and mRNA levels were significantly decreased in the transfected cells compared with the untransfected cells, which indicated that miR‑138 overexpression inhibited ISG15 expression. Additionally, the invasion, migration and proliferation abilities of successfully transfected CAL27 and SCC‑15 cells were significantly decreased compared with the untransfected cells (P<0.05). The results of the present study suggest that miR‑138 functions as a tumor‑suppressive miR and serves an important role in OSCC via regulating ISG15 expression. These findings suggest that miR‑138 is able to inhibit the proliferation, migration and invasion of OSCC cell lines.

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