2. Academic Validation
  3. Mechanism through which the hsa-circ_0000992- hsa- miR- 936-AKT3 regulatory network promotes the PM2.5-induced inflammatory response in human bronchial epithelial cells

Mechanism through which the hsa-circ_0000992- hsa- miR- 936-AKT3 regulatory network promotes the PM2.5-induced inflammatory response in human bronchial epithelial cells

  • Ecotoxicol Environ Saf. 2023 Dec 25:270:115778. doi: 10.1016/j.ecoenv.2023.115778.
Jing Lin Li 1,  Yi Tan 2,  Qiu Ling Wang 3,  Cai Xia Li 2,  Jin Chang Hong 2,  Hong Jie Wang 2,  Yi Wu 2,  De Chun Ni 2,  Xiao Wu Peng 4
Affiliations

Affiliations

  • 1 Nanning Center for Disease Control and Prevention, 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 Environment and Health Department, Shenzhen Center for Disease Control and Prevention, Shenzhen 518055, China.
  • 4 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: 38147774 DOI: 10.1016/j.ecoenv.2023.115778
Abstract

Background: Studies have shown that fine particulate matter (PM2.5) remains a significant problem in developing countries and plays a critical role in the onset and progression of respiratory illnesses. Circular RNAs (circRNAs) are involved in many pathophysiological processes,but their relationship to PM2.5 pollution is largely unexplored.

Objectives: To elucidate the functional role of hsa_circ_0000992 in PM2.5-induced inflammation in a human bronchial epithelial cell line (16HBE) and to clarify whether the competing endogenous RNA (ceRNA) mechanism is involved in the interrelationships between hsa_circ_0000992 and hsa-miR-936 and the inflammatory signaling pathways.

Methods: Detection of inflammatory factors in 16HBE cells exposed to PM2.5 by RT-qPCR and ELISA.High throughput sequencing and bioinformatics analysis methods were used to screen circRNA.The bioinformatics analysis method western blotting and dual-luciferase reporter gene system were used to verify mechanisms associated with circRNA.

Results: PM2.5 cause inflammation in the 16HBE cells. High throughput sequencing and RT-qPCR result revealed that the expression of hsa_circ_0000992 was markedly up-regulated in 16HBE exposed to PM2.5. The binding sites between hsa_circ_0000992 and hsa-miR-936 was confirmed by dual-luciferase reporter gene system.Western blotting and RT-qPCR showed that hsa_circ_0000992 can interact with hsa-miR-936 to regulate Akt serine/threonine kinase 3(Akt3),thereby activating the PI3K/Akt pathway and ultimately promoting the expression of interleukin (IL)- 1β and IL-8.

Conclusion: PM2.5 can induce the inflammatory response in 16HBE cells by activating the PI3K/Akt pathway. The expression of hsa_circ_0000992 increased when PM2.5 stimulated 16HBE cells,and the circRNA could then regulate the inflammatory response.Hsa_circ_0000992 regulates the hsa-miR-936/Akt3 axis through the ceRNA mechanism,thereby activating the PI3K/Akt signaling pathway,increasing the expression of cellular inflammatory factors,and promoting PM2.5-induced respiratory inflammation.

Keywords

Atmospheric fine particles; CeRNA; CircRNA; Human bronchial epithelial cells; Inflammatory response.

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