LncRNA NONMMUT055714 acts as the sponge of microRNA-7684-5p to protect against postoperative cognitive dysfunction

Postoperative cognitive dysfunction (POCD) is a neurological complication of surgery especially common in elderly patients. In this study, we investigated the role of NONMMUT055714 in POCD via regulation of miR-7684-5p. In a POCD mouse model, we induced overexpression of NONMUTT055714 via transfection of lentivrus into the hippocampus, and used the Morris water maze for assessment of cognitive function. Silencing of NONMUTT055714 and miR-7684-5p was induced in primary hippocampal neurons to observe the effects of these regulatory RNAs on cellular processes. Bioinformatics analysis and a double luciferase reporter experiment were performed to further explore the relationship between NONMMUT055714, miR-7684-5p, and SORLA. Cell and animal rescue experiments were performed to verify the ability of miR-7684-5p to reverse the protective effects of NONMMUT055714 overexpression in POCD. We observed that NONMMUT055714 has decreased expression in the POCD mouse model. Overexpression of NONMMUT055714 protected against cognitive impairment of the POCD mouse model in vivo. We identified miR-7684-5p as a NONMMUT055714-related miRNA and in turn as an upstream regulator of SORLA. We found that NONMMUT055714 downregulation is associated with decreased SORLA, increased Aβ and p-tau expression, increased inflammatory biomarkers, increased markers of oxidative stress, and increased neuronal apoptosis in vitro. The effects of NONMMUT055714 downregulation were reversed by silencing miR-7684-5p in vitro and in vivo. Taken together, our findings suggest that NONMMUT055714 is protective against the development of POCD via its function as a ceRNA (or miRNA sponge) in the regulation of miR-7684-5p and SORLA. We therefore propose NONMMUT055714 as a novel target for the investigation and prevention of POCD.