Abstract

Propofol (PPF), a commonly employed clinical anesthetic, has elicited growing concern due to its associated neurotoxic effects. However, the functional role and mechanistic insights of microRNA-3909 (miR-3909) in PPF-induced neurotoxicity remain unexplored. This study sought to elucidate the expression of miR-3909 and its underlying molecular mechanisms in the context of PPF-induced neurotoxicity. An in vitro model of  PPF neurotoxicity was established using SH-SY5Y cells (PPF-SH-SY5Y). Initial assessments via cell counting kit-8 (CCK-8) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) demonstrated that treatment with 50 µM PPF significantly reduced cell viability and downregulated miR-3909 expression. Subsequent functional assays revealed that overexpression of miR-3909 effectively alleviated PPF-induced neurotoxicity, as evidenced by enhanced cell viability, suppression of apoptosis, reduced lactate dehydrogenase (LDH) release, and decreased reactive oxygen species (ROS) levels. Mechanistic investigations, including a dual-luciferase reporter assay, validated that miR-3909 directly targets and negatively regulates the expression of polymerase I and transcript release factor (PTRF). Notably, PTRF was significantly upregulated in PPF-SH-SY5Y cells, and overexpression of PTRF substantially counteracted the neuroprotective effects mediated by miR-3909. Collectively, these findings indicate that miR-3909 alleviates propofol-induced neurotoxicity by targeting PTRF, thereby providing a potential therapeutic target for this condition.