Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck neoplasm. Down-regulation of hsa-microRNA-378 (miR-378) has been proved in OSCC tissues, suggesting that miR-378 might play crucial roles in the progression of OSCC. The present study aimed to evaluate the effect of miR-378-3p/5p on the proliferation and apoptosis of OSCC in vitro and in vivo. According to the results, lentivirus-mediated overexpression of miR-378 lowered the colony formation efficiency, blocked cell cycle progression, and decreased the percentage of Ki-67 positive cells, whereas knockdown of miR-378-3p/5p led to the opposite results. Furthermore, the apoptosis of OSCC cells was induced by the overexpression of miR-378 as evidenced by decreasing Bcl-2/Bax ratio, increasing cleaved caspase-9, cleaved caspase-3, and cleaved PARP levels, and promoting the release of cytochrome c into the cytoplasm. However, the above results were reversed by miR-378-3p/5p silencing. In addition, the overexpression of miR-378 inhibited the activation of PI3K/AKT signalling pathway. Conversely, miR-378-3p/5p knockdown resulted in the inactivation of PI3K/AKT signalling pathway. Mechanically, we validated that miR-378-3p/5p could target kallikrein-related peptidase 4 (KLK4), and enforced overexpression of KLK4 counteracted miR-378 overexpression-induced apoptosis. Finally, tumourigenesis in nude mice was suppressed by the overexpression of miR-378, which was promoted by miR-378-3p/5p silencing. Taken together, these results suggest that miR-378 may be a potential target in the diagnoses and treatment of OSCC.
Keywords: KLK4; apoptosis; miR-378; oral squamous cell carcinoma; proliferation.
© 2019 John Wiley & Sons Australia, Ltd.