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miRNA-6515-5p regulates particulate matter-induced inflammatory responses by targeting CSF3 in human bronchial epithelial cells

Authors
Son, Eun SukKo, Ui WonJeong, Hee-YeonPark, So YoungLee, Young EunPark, Jeong-WoongJeong, Sung HwanKim, Se-HeeKyung, Sun Young
Issue Date
Oct-2022
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Keywords
CSF3; ERK; inflammation; microRNA; Particulate matter
Citation
Toxicology in Vitro, v.84
Journal Title
Toxicology in Vitro
Volume
84
URI
https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/86888
DOI
10.1016/j.tiv.2022.105428
ISSN
0887-2333
Abstract
Particulate matter (PM) is associated with the incidence, exacerbation, and mortality of variable respiratory diseases. However, the molecular mechanisms of PM10-mediated inflammation are unclear. We identified microRNAs (miRNAs) and messenger RNAs (mRNAs) related to the inflammatory response in PM10-exposed bronchial epithelial cells using next-generation sequencing. Of the miRNAs, miR-6515-5p was significantly downregulated in PM10-exposed human bronchial epithelial BEAS-2B cells. miR-6515-5p regulated the production of pro-inflammatory cytokines (IL-6 and IL-8) and the expression of inflammatory genes (IL-1β, IL-6, IL-8, TNF-α, CXCL-1, and MCP-1) via MAPK/ERK signaling; overexpression of miR-6515-5p using a mimic inhibited PM10-induced inflammatory responses via inactivation of the ERK pathway, whereas downregulation of miR-6515-5p via an inhibitor significantly increased inflammation in PM10-exposed cells via activation of ERK. Furthermore, we identified colony stimulating factor 3 (CSF3) as a target gene of miR-6515-5p using TargetScanHuman, and confirmed the association between miR-6515-5p and CSF3 using a luciferase reporter assay. Furthermore, we found that mRNA and protein levels of CSF3 were negatively regulated by miR-6515-5p. Inhibition of CSF3 by small interfering RNA significantly reduced the expression and production of inflammatory markers in PM10-exposed cells by inactivating the MAPK/ERK signaling pathway. Therefore, we suggest that miR-6515-5p regulates PM10-induced inflammatory responses by targeting CSF3 via MAPK/ERK signaling in bronchial epithelial cells.
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