lncRNA AABR07005593.1 potentiates PM2.5-induced interleukin-6 expression by targeting MCCC1

  • Ecotoxicol Environ Saf. 2021 Dec 15;226:112834. doi: 10.1016/j.ecoenv.2021.112834.
FangPing Liao  1 ,  Yi Tan  2 ,  YuYu Wang  2 ,  CaiLan Zhou  3 ,  QiuLing Wang  4 ,  JingLin Li  4 ,  LiMei He  2 ,  XiaoWu Peng  5
Affiliations
  • 1. State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510535, China; School of Public Health, Guangxi Medical University, Nanning 530021, China.
  • 2. State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510535, China.
  • 3. School of Public Health and Management, YouJiang Medical University for Nationalities, Baise 533000, China.
  • 4. School of Public Health, Guangxi Medical University, Nanning 530021, China.
  • 5. State Environmental Protection Key Laboratory of Environmental Pollution Health Risk Assessment, South China Institute of Environmental Sciences, Ministry of Ecology and Environment, Guangzhou 510535, China. Electronic address: [email protected].
PMID: 34619471 DOI: 10.1016/j.ecoenv.2021.112834
Abstract

Background: Fine particle pollution, specifically pollution by fine particulate matter (PM2.5), remains a significant concern in developing countries and plays an important role in the development and progression of respiratory diseases. Increasing evidences have demonstrated that long non-coding RNAs (lncRNAs) may act as vital molecules by binding to specific RNA-binding protein (RBP); however, their relationship with PM2.5 pollution is largely unexplored.

Objective: We investigated the association between lncRNA and respiratory system inflammation caused by PM2.5.

Methods: PM2.5 components were detected by gas chromatography-mass spectrometry (GC-MS), inductively coupled plasma-mass spectrometry (ICP-MS), and ionic chromatography. We established an inflammation model of PM2.5-induced toxicity in vivo (male and female SD rats, 0, 25, 50 and 100 mg/k PM2.5, 1, 7 and 14 days, single non-invasive tracheal instillation) and in vitro (rat alveolar macrophage cell line (NR8383), 0, 50, 100, 200, 400 μM PM2.5 for 24, 48, and 72 h). lncRNA high-throughput Sequencing (lncRNA-seq) was used to investigate lncRNA profiles in PM2.5-treated NR8383 cells, and RNA interference (RNAi) was applied to explore the function of the target lncRNA. The mechanisms associated with specific lncRNAs were explored using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) and western blot.

Results: PM2.5-treated NR8383 cells and SD rats exhibited respiratory inflammation. lncRNA AABR07005593.1 was a pro-inflammatory factor that regulated IL-6 levels. Mechanistically, ChIRP-MS and western blot analyses revealed that highly expressed lncRNA AABR07005593.1 interacted with MCCC1 to involve in the activation of NF-κB pathway, and ultimately promoted the expression of IL-6.

Conclusion: This study demonstrated that PM2.5 induced inflammation in vivo and in vitro. Furthermore, lncRNA AABR07005593.1 bound to MCCC1 to potentiated IL-6 expression. Therefore, lncRNA AABR07005593.1 may act as a potential biomarker for PM2.5 inflammation.

Keywords
PM(2.5); Respiratory inflammation; lncRNA AABR07005593.1.
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