CircRNA1149 from Apostichopus japonicus suppresses coelomocyte apoptosis act as miR-92a sponge to regulate Bax expression in response to Vibrio splendidus infection

Abstract

Circular RNAs (circRNAs) are a class of widespread and diverse covalently closed circular endogenous RNAs that play pivotal roles in mediating immune regulation in mammals. However, the function and regulatory mechanisms of circRNAs in lower invertebrates are still far unidentified. In this study, we discovered a circRNA derived from AJAPscaffold1149: 133758|203,802 of Apostichopus japonicus genome, termed circRNA1149 (circ1149), that is closely related to the occurrence of skin ulcer syndrome (SUS) in sea cucumber A. japonicus. Results revealed that circ1149 plays a significant role in pathogen Vibrio splendidus-induced coelomocyte apoptosis in sea cucumbers. Our study also found a microRNA miR-92a, which could promote coelomocyte apoptosis caused by V. splendidus via targeting Bcl-2-associated X protein (Bax). And, Bax is the first identified pro-apoptotic member of the Bcl-2 protein family. Moreover, we detected that the increased coelomocyte apoptosis level and Bax protein level by circ1149 silencing in response to pathogen infection could be partly recovered by miR-92a inhibitors in vivo and in vitro. Our data indicated that circ1149 functions as a competing endogenous RNA (ceRNA) of Bax by competing for adsorbing miR-92a, thereby suppressing the coelomocyte apoptosis levels induced by V. splendidus. The overall results of this study suggested that circ1149 plays a crucial role in regulating the innate immune response of sea cucumbers, and provides a new insight for understanding the functions of circRNAs in lower invertebrates in response to bacterial infection.