Overexpression of miR-874-3p alleviates LPS-induced apoptosis and inflammation in alveolar epithelial cell by targeting EGR3/NF-κB

  • Huirun Yang Pediatrics of Integrated Traditional Chinese and Western Medicine, Zhejiang Zhoushan Putuo District Hospital of Traditional Chinese Medicine, Zhoushan, Zhejiang Province, 316100, China
  • Yang Dong Department of Pediatrics, People’s Hospital of Baoshan City, Baoshan, Yunnan Province, 678000, China
  • Yan Zhou Department of Pediatrics, People’s Hospital of Baiyun District, Guiyang City, Guizhou Province, 510440, China
  • Huajun Li Department of Infection, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China https://orcid.org/0000-0003-4455-6193


Objective: MicroRNA (miRNA) is implicated in the pathogenic mechanism of pneumonia. Role of miR-874-3p in pediatric pneumonia was therefore evaluated in this study. Methods: Expression levels of miR-874-3p in the serum samples from pediatric patients with pneumonia and LPS-treated HPAEpiC were determined by RT-qPCR (reverse transcription quantitative real-time PCR). Secretion of inflammatory factors in LPS-treated HPAEpiC were determined by qRT-PCR and ELISA. Cell viability and apoptosis were evaluated by CCK8 and flow cytometry, respectively. HPAEpiC was used for the validation of binding target of miR-874-3p. Mechanism was determined by NF-κB promoter activity assay. Results: MiR-874-3p was reduced in serum samples of pediatric patients with pneumonia, and LPS treatment dose-dependently decreased miR-874-3p expression in HPAEpiC. TNF-α and IL-1β expression levels were increased in HPAEpiC post LPS treatment. Over-expression of miR-874-3p attenuated LPS-induced increase of TNF-α and IL-1β and reversed LPS-induced decrease of cell viability and increase of cell apoptosis in HPAEpiC. EGR3 (early growth response 3), increased in LPS-induced HPAEpiC, was a target gene of miR-874-3p. EGR3 over-expression reversed miR-874-3p over-expression-induced increase of cell viability, decrease of cell apoptosis, TNF-α and IL-1β in LPS-induced HPAEpiC. Over-expression of miR-874-3p reduced p65 expression and NF-κB promoter activity in LPS-induced HPAEpiC, while EGR3 over-expression reversed these suppressive effects. Conclusion: MiR-874-3p negatively regulates EGR3 expression to promote cell viability and inhibit apoptosis as well as inflammation in LPS-treated HPAEpiC via suppression of NF-κB pathway, suggesting a potential therapeutic strategy for pneumonia.