Effects of microRNA­338­3p on morphine­induced 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. Freshly­isolated mouse peritoneal macrophages were cultured in vitro and treated with MP following transfection with miR­338­3p mimic, inhibitor or controls. miR­338­3p expression levels increased significantly following MP treatment (P<0.01). This increase was enhanced following transfection with miR­338­3p mimic (P<0.05) and abrogated following transfection with miR­338­3p 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 miR­338­3p inhibitor (P<0.05). Bioinformatics software predicted that sex determining region Y­box 4 (SOX4) was the target gene of miR­338­3p and this was verified using a dual­luciferase 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 miR­338­3p inhibitor (P<0.05). Caspase­3 protein expression levels increased markedly following MP treatment (P<0.05); however, this increase was inhibited by transfection with miR­338­3p inhibitor (P<0.05). Therefore, decreased expression of miR­338­3p may suppress MP­induced apoptosis, potentially via the upregulation of SOX4 expression and the caspase­3­dependent apoptotic signaling pathway.