Effects of microRNA‑338‑3p on morphine‑induced apoptosis and its underlying mechanisms.

The aim of the present study was to investigate the effects of microRNA-338-3p (miR-338-3p) on morphine (MP)-induced apoptosis, and its underlying mechanisms. Freshly‑isolated mouse peritoneal macrophages were cultured in vitro and treated with MP following transfection with miR‑338‑3p mimic, inhibitor or controls. miR‑338‑3p expression levels increased significantly following MP treatment (P<0.01). This increase was enhanced following transfection with miR‑338‑3p mimic (P<0.05) and abrogated following transfection with miR‑338‑3p inhibitor (P<0.05). The apoptotic rate increased significantly in groups treated with MP (P<0.05); however, this increase was abrogated by transfection with miR‑338‑3p inhibitor (P<0.05). Bioinformatics software predicted that sex determining region Y‑box 4 (SOX4) was the target gene of miR‑338‑3p and this was verified using a dual‑luciferase reporter gene system. SOX4 mRNA and protein expression levels decreased significantly following MP treatment (P<0.05); however, this decrease was abrogated following transfection with miR‑338‑3p inhibitor (P<0.05). Caspase‑3 protein expression levels increased markedly following MP treatment (P<0.05); however, this increase was inhibited by transfection with miR‑338‑3p inhibitor (P<0.05). Therefore, decreased expression of miR‑338‑3p may suppress MP‑induced apoptosis, potentially via the upregulation of SOX4 expression and the caspase‑3‑dependent apoptotic signaling pathway.