Exploring the Clinical Significance and Mechanistic Role of the LINC00487/hsa-miR-663b Axis in Cell Line Models of Acute Lung Injury.

Abstract

Acute lung injury (ALI) is a serious lung disease that tends to progress to acute respiratory distress syndrome (ARDS). This study was aimed to seek new biomarkers of ALI to provide a basis for monitoring the progress of ALI in time. A human bronchial epithelial cell line (HBEC3-KT) was treated with 1 μg/ml lipopolysaccharide (LPS) to induce the ALI response. The expression of LINC00487 and hsa-miR-663b in LPS-treated HBEC3-KT cells was detected by RT-qPCR. The regulation of hsa-miR-663b by LINC00487 was investigated using a dual luciferase assay and an over-expression experiment. Cell proliferation and apoptosis were detected by the CCK-8 assay and annexin V-FITC kit. Serum levels of LINC00487 and hsa-miR-663b were detected by collecting blood samples from ALI patients (with or without ARDS), and the ROC curve was constructed to assess their clinical value in ALI. LPS inhibited proliferation of HBEC3-KT cells and promoted their apoptosis and inflammatory response, which were further enhanced by LINC00487 over-expression and reversed by an hsa-miR-663b mimic. The hsa-miR-663b mimic weakened the luciferase activity of HBEC3-KT cells transfected with the luciferase vector of wild-type LINC00487. The cellular level of hsa-miR-663b was down-regulated by LINC00487 over-expression and increased by LINC00487 knockdown. The ROC curve showed that LINC00487 combined with hsa-miR-663b effectively diagnosed ALI (AUC = 0.840) and was a classifier for ALI patients with or without ARDS (AUC = 0.822). Serum LINC00487 and hsa-miR-663b levels are valuable biomarkers of ALI and can monitor the ALI progress. LINC00487 may promote ALI progression by negatively regulating hsa-miR-663b.