title: miR-31 Links Lipid Metabolism and Cell Apoptosis in Bacteria-ChallengedApostichopus japonicus viaTargeting CTRP9.
abstract: The biological functions of microRNAs (miRNAs) have been studied in a number of eukaryotic species. Recent studies on vertebrate animals have demonstrated critical roles of miRNA in immune and metabolic activities. However, studies on the functions of miRNA in invertebrates are very limited. Here, we demonstrated that miR-31 fromApostichopus japonicusdisrupts the balance of lipid metabolism, thus resulting in cell apoptosis by targeting complement C1q tumor necrosis factor-related protein 9 (AjCTRP9), a novel adipokine with pleiotropic functions in immunity and metabolism. Lipidomic analysis suggested that the intercellular lipid metabolites were markedly altered, and three ceramide (Cer) species synchronously increased in the AjCTRP9-silenced coelomocytes. Moreover, exogenous Cer exposure significantly induced apoptosis in the coelomocytesin vivo, in agreement with findings from miR-31 mimic- orAjCTRP9small-interfering RNA-transfected coelomocytes. Furthermore, we found that the imbalance in sphingolipid metabolism triggered by the overproduction of Cers ultimately resulted in the activation of the apoptosis initiator caspase-8 and executioner caspase-3. Our findings provide the first direct evidence that miR-31 negatively modulates the expression ofAjCTRP9and disturbance of Cer channels, thus leading to caspase-3- and caspase-8-dependent apoptosis, during the interactions between pathogens and host.
authors.affiliation: School of Marine Sciences, Ningbo University , Ningbo , China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Shao
authors.affiliation: School of Marine Sciences, Ningbo University , Ningbo , China.
authors.forename: Chenghua
authors.initials: C
authors.lastname: Li
authors.affiliation: Agricultural Center, Louisiana State University , Baton Rouge, LA , USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Marine Sciences, Ningbo University , Ningbo , China.
authors.forename: Pengjuan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: School of Marine Sciences, Ningbo University , Ningbo , China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Marine Sciences, Ningbo University , Ningbo , China.
authors.forename: Xuelin
authors.initials: X
authors.lastname: Zhao
keywords: Apostichopus japonicus; apoptosis; ceramide; complement C1q tumor necrosis factor-related protein 9; lipidomics; miR-31