Virulence 2024 Dec 18;151:2367660. doi: 10.1080/21505594.2024.2367660.

HIF-1α interacting with miR-2013-3p regulates pathogen-induced energy production changes via targeting glutamate dehydrogenase in the sea urchin Strongylocentrotus intermedius.

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To investigate the functions of hypoxia inducible factor-1α (HIF-1α) homologs, we cloned and characterized the full-length cDNA of a novel HIF-1α homolog (SinHIF-1α) from the sea urchin Strongylocentrotus intermedius. We then explored the functions of SinHIF-1α and its regulatory factor (miR-2013-3p) in the pathogen-induced metabolic response of S. intermedius. The results showed the following: 1) The full-length cDNA of SinHIF-1α was 4265 bp, with a high level of sequence conservation across the phylum Echinodermata. 2) MiR-2013-3p could bind to the 3'-UTR of SinHIF-1α and negatively regulate the expression of SinHIF-1α in S. intermedius. 3) Both SinHIF-1α silencing and miR-2013-3p overexpression suppressed the relative content of adenosine triphosphate (ATP) in coelomocytes as well as the relative expression (mRNA and protein) and total enzyme activity of glutamate dehydrogenase (GDH) in S. intermedius. 4) The miR-2013-3p/SinHIF-1α axis may regulate ATP production at 6-24 h and 48-72 h post-pathogen infection through accompanied by alterations in the relative expression and enzyme activity of GDH in S. intermedius. In summary, all observations from this study indicated that the pathogen utilizes the miR-2013-3p/SinHIF-1α axis to reduce ATP production and thereby attenuate the antimicrobial capability of the host via targeting GDH.

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