LincRNA00612 inhibits apoptosis and inflammation in LPS-induced BEAS-2B cells via enhancing interaction between p-STAT3 and A2M promoter

PeerJ. 2023 Mar 2:11:e14986. doi: 10.7717/peerj.14986. eCollection 2023.

Abstract

Long non-coding RNAs (lncRNAs) have been reported as key regulators of chronic obstructive pulmonary disease (COPD). This study aimed to figure out the regulatory mechanism as well as the effects of lncRNA00612 (LINC00612) in lipopolysaccharide (LPS)-induced inflammation and apoptosis in BEAS-2B cells. LINC00612 and its co-expressed gene alpha-2-macroglobulin (A2M) were strikingly downregulated in the peripheral venous blood of COPD patients. Overexpressed LINC00612 enhances BEAS-2B cells against apoptosis and inflammatory reactions mediated by LPS, however, an A2M knockdown can attenuate the degree of the enhancement. Bioinformatics analysis revealed putative binding sites between LINC00612, signal transducer and activator of transcription 3 (STAT3) and the A2M promoter, while RNA antisense purification and Chromatin immunoprecipitation were performed to confirm the prediction. Knockdown of LINC00612 impaired the binding of p-STAT3 to the promoter of A2M, which meant that LINC00612 was critical for the binding of STAT3 with the A2M promoter. Therefore, it can be concluded that LINC00612 ameliorates LPS-induced cell apoptosis and inflammation via recruiting STAT3 to bind to A2M. This conclusion will serve as a theoretical foundation for the treatment of COPD.

Keywords: Alpha-2-macroglobulin; Chronic obstructive pulmonary disease; LINC00612; Signal transducer and activator of transcription 3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / physiology
  • Cell Line
  • Humans
  • Inflammation* / chemically induced
  • Inflammation* / genetics
  • Inflammation* / metabolism
  • Lipopolysaccharides / adverse effects
  • Lipopolysaccharides / pharmacology
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Pulmonary Disease, Chronic Obstructive* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • STAT3 Transcription Factor* / genetics
  • STAT3 Transcription Factor* / metabolism
  • alpha-Macroglobulins* / genetics
  • alpha-Macroglobulins* / metabolism

Substances

  • A2M protein, human
  • alpha-Macroglobulins
  • Lipopolysaccharides
  • RNA, Long Noncoding
  • STAT3 protein, human
  • STAT3 Transcription Factor

Grants and funding

This study was supported by grants from the Jiangsu Province Social Development Project (BE2020651 to Qian Zhang), the Jiangsu Province “333 Talents” Project (BRA2020015 to Qian Zhang), the Changzhou Sci & Tech Program (CE20205023 to Qian Zhang), the China Postdoctoral Science Foundation (2020M670011ZX to Zhengdao Mao), the Sci & Tech Project for Young Talents of Changzhou Health Commission (WZ202010 to Yujia Shi) and Changzhou Healthy Seedling Talent Training Project (CZQM2020077 to Yujia Shi). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.