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

Ling-Xia Li; Yuan-Jun Li; Jia-Xuan He

doi:10.1002/jcb.27513

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

J Cell Biochem. 2019 Feb;120(2):2058-2069. doi: 10.1002/jcb.27513. Epub 2018 Sep 23.

Authors

Ling-Xia Li¹, Yuan-Jun Li¹, Jia-Xuan He²

Affiliations

¹ Anesthesia Department, Yanan University Affiliated Hospital, Yanan, Shaanxi, China.
² Respiratory Medicine Department, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

PMID: 30246300
DOI: 10.1002/jcb.27513

Abstract

Background and objectives: In this study, we aimed to study the molecular mechanisms underlying the symptoms of hyperresponsiveness during intubation.

Method: 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).

Results: 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.

Conclusion: 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.

Keywords: hyperresponsiveness upon intubation; long noncoding RNA-prognosis-associated gallbladder cancer (LncRNA-PAGBC); miR-511; nitric oxide (NO); nitric oxide synthase 1 (NOS1).