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.

环状 RNA (circRNA) 是一类广泛存在且多样化的共价闭合环状内源性 RNA，在哺乳动物免疫调节中发挥关键作用。然而，circRNA在低等无脊椎动物中的功能和调控机制仍远未确定。在本研究中，我们发现了一种来源于刺参基因组AJAPscaffold1149: 133758|203,802的circRNA，称为circRNA1149（circ1149），与刺参皮肤溃疡综合征（SUS）的发生密切相关。结果表明，circ1149在病原体华丽弧菌诱导的海参体腔细胞凋亡中起重要作用。我们的研究还发现了一种 microRNA miR-92a，它可以促进由V. splendidus 通过靶向 Bcl-2 相关 X 蛋白 (Bax)。而且，Bax 是 Bcl-2 蛋白家族中第一个确定的促凋亡成员。此外，我们检测到通过 circ1149 沉默响应病原体感染而增加的体腔细胞凋亡水平和 Bax 蛋白水平可以通过 miR-92a 抑制剂在体内和体外部分恢复。我们的数据表明，circ1149 通过竞争吸附 miR-92a 作为 Bax 的竞争性内源性 RNA (ceRNA)，从而抑制由V. splendidus诱导的体腔细胞凋亡水平. 本研究的总体结果表明，circ1149在调节海参的先天免疫反应中发挥着至关重要的作用，并为了解低等无脊椎动物中circRNAs应对细菌感染的功能提供了新的见解。