miR-616-3p alleviates inflammatory response by targeting C-X-C motif chemokine ligand 5
- 주제(키워드) CHOP , CXCL5 , Inflammation , Lung epithelial cells , miR-616
- 등재 SCIE, SCOPUS
- 발행기관 Elsevier B.V.
- 발행년도 2024
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000213578
- 본문언어 영어
- Published As https://doi.org/10.1016/j.bbrc.2023.149335
- PubMed 38042032
초록/요약
C/EBP homologous protein (CHOP) is a key regulator in ER stress-mediated signaling pathway via PERK-dependent unfolded protein response. It has been known that microRNA-616 (miR-616) is produced from the intron of the human DDIT3 gene encoding CHOP and increased by ER stress. However, the role of miR-616 and its targets are not fully addressed yet. Here we try to identify a novel target of miR-616 in human lung epithelial cells. Microarray analysis showed that CXCL5 is the most downregulated gene by miR-616 overexpression in A549 cells. We also found that CXCL5 mRNA and protein levels were significantly reduced by miR-616 mimic in the presence or absence of TNFα, while anti-miR-616 enhanced CXCL5 expression. In addition, miR-616-3p targeting sequence in 3′UTR of CXCL5 was confirmed by luciferase reporter assay suggesting that miR-616-3p directly binds to 3′UTR of CXCL5 and inhibits CXCL5 expression. Finally, we confirmed that conditioned medium from A549 cells treated with TNFα or Streptococcus pneumoniae lysates increased intra-alveolar neutrophil infiltration in a mouse model of pulmonary inflammation, while this induction was significantly reduced in a conditioned medium from cells transfected with miR-616-3p. These results suggest that miR-616-3p can alleviate CXCL5-induced pulmonary inflammatory response via targeting 3′UTR of CXCL5 gene. © 2023 Elsevier Inc.
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