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

Biochem Biophys Res Commun. 2024 Jan 8:691:149335. doi: 10.1016/j.bbrc.2023.149335. Epub 2023 Nov 28.

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.

Keywords: CHOP; CXCL5; Inflammation; Lung epithelial cells; miR-616.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Chemokines / genetics
  • Culture Media, Conditioned
  • Humans
  • Ligands
  • Mice
  • MicroRNAs* / metabolism
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • 3' Untranslated Regions
  • Culture Media, Conditioned
  • Ligands
  • Chemokines
  • MIRN616 microRNA, human