Mechanism through which the hsa-circ_0000992- hsa- miR- 936-AKT3 regulatory network promotes the PM 2.5 -induced inflammatory response in human bronchial epithelial cells.

Background: Studies have shown that fine particulate matter (PM _2.5 ) 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 PM _2.5 pollution is largely unexplored.
Objectives: To elucidate the functional role of hsa_circ_0000992 in PM _2.5 -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 PM _2.5 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: PM _2.5 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 PM _2.5 . 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: PM _2.5 can induce the inflammatory response in 16HBE cells by activating the PI3K/AKT pathway. The expression of hsa_circ_0000992 increased when PM _2.5 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 PM _2.5 -induced respiratory inflammation.
Competing Interests: Declaration of Competing Interest We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)