Long noncoding RNA PAGBC contributes to nitric oxide (NO) production by sponging miR-511 in airway hyperresponsiveness upon intubation.

Abstract

In this study, we aimed to study the molecular mechanisms underlying the symptoms of hyperresponsiveness during intubation. The value of circulating long noncoding RNA (lncRNA)-prognosis-associated gallbladder cancer (PAGBC) in the prediction of hyperresponsiveness upon intubation during general anesthesia was evaluated via the receiver operating characteristic analyses of serum miR-511, serum PAGBC, and serum nitric oxide (NO). In addition, the possible association between lncRNA-PAGBC/NOS1 messenger RNA (mRNA) and miR-511 was further validated via real-time quantitative polymerase chain reaction, immunohistochemistry assay, computational analysis, and luciferase assay. Enzyme-linked immunosorbent assay and Western blot analysis were also conducted to establish the regulatory relationship among PAGBC, miR-511, and NO synthase 1 (NOS1). Compared with circulating miR-511 and serum NO, circulating PAGBC was associated with a higher predictive value. In addition, a negative correlation was found between serum miR-511 and serum PAGBC (multicorrelation coefficient: -0.5) as well as between serum miR-511 and serum NO (multicorrelation coefficient: -0.6). In addition, both lncRNA-PAGBC and NO were decreased in patients with hyperresponsiveness, whereas the levels of miR-511 and NOS1 in these patients were similar to those in normal patients. Furthermore, our computational analyses and luciferase assays validated the direct binding between miR-511 and lncRNA-PAGBC, whereas NOS1 mRNA was identified as a virtual target gene of miR-511. Moreover, in the presence of lncRNA-PAGBC, we also observed an evident increase in the levels of NOS1 and NO accompanied by an obvious decrease of miR-511 expression. LncRNA-PAGBC downregulated the expression of miR-511, which in turn upregulated the expression of NOS1 mRNA and led to the increase in NOS1 expression, thus leading to the inhibited responsiveness (normal-responsiveness rather than hyperresponsiveness) to intubation in patients.