Title : LINCRNA00612 inhibits apoptosis and inflammation in lps- induced beas- 2B cells via enhancing interaction between p- STAT3 and a2M promoter
Abstract:
Long non-coding RNAs (lncRNAs) have been reported as key regulators of chronic obstructive pulmonary disease (COPD). However, the specific mechanisms have not been fully understood. This study aimed to establish the effects and regulatory mechanism of lncRNA00612 (LINC00612) in lipopolysaccharide (LPS)-induced apoptosis and inflammation in BEAS-2B cells. The expression levels of LINC00612 and alpha-2-macroglobulin (A2M) were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expressions of apoptosis-associated proteins, caspase3 protein, signal transducer and activator of transcription 3 (STAT3) protein and A2M protein were determined by western blot. Cell viability was illustrated by cell counting kit-8 (CCK-8) assay. Cell apoptosis was investigated by flow cytometer assay. Inflammatory factor was demonstrated by enzyme-linked immunosorbent assay (ELISA). The binding sites between LINC00612, STAT3 and A2M promoter were predicted by catRAPID and JASPAR, while RNA antisense purification and Chromatin immunoprecipitation were performed to confirm the prediction. LINC00612 and A2M expressions were strikingly downregulated in the peripheral venous blood of COPD patient and LPS-induced BEAS-2B cells, when compared to control groups. LINC00612 overexpression promoted BEAS-2B cells against LPS-mediated apoptosis and inflammation, whereas these effects were attenuated by A2M knockdown. Mechanistically, LINC00612 promoted the transcription of A2M by recruiting STAT3 to bind to A2M promoter. LINC00612 ameliorates LPS-induced cell apoptosis and inflammation via recruiting STAT3 to bind to A2M. This finding will provide a theoretical basis for the treatment of COPD.
Audience Take Away Notes:
- The specific mechanisms of COPD have not been fully understood. Increasing evidence suggested that lncRNAs played an important role in a variety of diseases including COPD. In the present study, we were committed to elucidating the regulatory relationship between LINC00612, STAT3, and A2M, and their specific role in the pathogenesis of COPD.
- The present study illuminated the role of LINC00612 in COPD and confirmed the possibility of LINC00612 as a biomarker for diagnosis of COPD.
- Our research demonstrated that the binding site of STAT3 to the A2M promoter in human healthy lung epithelial cell lines (BEAS-2B) and revealed that LINC00612 could bind p-STAT3 and enhance subsequent A2M gene transcription, suggesting the presence of a novel mode of A2M
