2. Academic Validation
  3. linc01515 regulates PM2.5-induced oxidative stress via targeting NRF2 in airway epithelial cells

linc01515 regulates PM2.5-induced oxidative stress via targeting NRF2 in airway epithelial cells

  • Environ Pollut. 2023 May 9;121798. doi: 10.1016/j.envpol.2023.121798.
Xi Wang 1,  Huanhuan Zhu 1,  Guanting Sun 1,  Meiyu Zhou 1,  Huilin Zhang 1,  Hanting Liu 1,  Meilin Wang 1,  Zhengdong Zhang 1,  Haiyan Chu 2
Affiliations

Affiliations

  • 1 Department of Environmental Genomics, Institute of Healthy Jiangsu Development, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
  • 2 Department of Environmental Genomics, Institute of Healthy Jiangsu Development, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center of Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. Electronic address: [email protected].
PMID: 37169236 DOI: 10.1016/j.envpol.2023.121798
Abstract

Dysregulation of long non-coding RNA (lncRNA) is involved in the adverse effects caused by fine particulate matter (PM2.5). However, the molecular mechanism is not fully clarified. In this study, we performed lncRNA sequencing on PM2.5-treated human bronchial epithelial (HBE) cells to identify vital lncRNA, and verified the differential expression of the lncRNA by RT-qPCR in HBE and human normal lung epithelial (BEAS-2B) cells. A total of 657 and 652 lncRNAs were dysregulated after exposure to 125 and 250 μg/mL of PM2.5, respectively. Of these, lncRNA linc01515 was upregulated in HBE and BEAS-2B cells with PM2.5 treatment. Subcellular localization experiments showed that linc01515 was mostly localized in the nucleus. Functionally, we downregulated the expression of linc01515 in HBE and BEAS-2B cells before PM2.5 treatment, which can decrease malonydialdehyde (MDA) and Reactive Oxygen Species (ROS) levels, and improve superoxide dismutase (SOD) activity. Correspondingly, linc01515 overexpression enhanced PM2.5-induced oxidative injury in airway epithelial cells. Mechanistically, N6-methyladenosine RNA binding protein immunoprecipitation (MeRIP) assay showed that the enrichment level of m6A on linc01515 was increased after PM2.5 treatment, and the expression of linc01515 was decreased with 3-deazaadenosine (DAA) to inhibit the RNA methylation level. Western Blot found that NRF2, a vital transcription factor, was enhanced remarkably in linc01515-silenced cells and decreased in linc01515-overexpressed cells. Furthermore, inhibition of NRF2 activity significantly rescued effect of downregulated linc01515 expression on PM2.5-induced cytotoxicity. In addition, we observed the similar effect when downregulating linc01515 and NRF2 expression in HBE and BEAS-2B cells before PM2.5 treatment. Taken together, our findings demonstrated that PM2.5 treatment may boost the expression of linc01515 by enhancing its m6A modification, and then regulate NRF2 to induce oxidative damage of airway epithelial cells.

Keywords

N(6)-methyladenosine; NRF2; Oxidative stress; PM(2.5); linc01515.

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