miR-616-3p alleviates inflammatory response by targeting C-X-C motif chemokine ligand 5

Suyeon Lee, Suji Kim, Tae Jin Lee, Jae Hyang Lim, Chang Hoon Woo

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number149335
JournalBiochemical and Biophysical Research Communications
Volume691
DOIs
StatePublished - 8 Jan 2024

Bibliographical note

Publisher Copyright:
© 2023 Elsevier Inc.

Keywords

  • CHOP
  • CXCL5
  • Inflammation
  • Lung epithelial cells
  • miR-616

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