CircArid4b: A novel circular RNA regulating antibacterial response during hypoxic stress via apoptosis in yellow catfish (Pelteobagrus fulvidraco)

Linxin Zhou; Jiayi Li; Xinxin Sun; Yingying Xin; Shaowu Yin; Xianhui Ning

doi:10.1016/j.cbpc.2025.110121

CircArid4b: A novel circular RNA regulating antibacterial response during hypoxic stress via apoptosis in yellow catfish (Pelteobagrus fulvidraco)

Comp Biochem Physiol C Toxicol Pharmacol. 2025 Jan 7:289:110121. doi: 10.1016/j.cbpc.2025.110121. Online ahead of print.

Authors

Linxin Zhou¹, Jiayi Li¹, Xinxin Sun¹, Yingying Xin¹, Shaowu Yin², Xianhui Ning³

Affiliations

¹ Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Jiangsu Key Laboratory of Ocean-Land Environmental Change and Ecological Construction, School of Marine Science and Engineering, Nanjing Normal University, Nanjing 210023, Jiangsu, China.
² Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Jiangsu Key Laboratory of Ocean-Land Environmental Change and Ecological Construction, School of Marine Science and Engineering, Nanjing Normal University, Nanjing 210023, Jiangsu, China; Co-Innovation Center for Marine Bio-Industry Technology of Jiangsu Province, Lianyungang 222005, China.
³ Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Jiangsu Key Laboratory of Ocean-Land Environmental Change and Ecological Construction, School of Marine Science and Engineering, Nanjing Normal University, Nanjing 210023, Jiangsu, China; Co-Innovation Center for Marine Bio-Industry Technology of Jiangsu Province, Lianyungang 222005, China. Electronic address: [email protected].

PMID: 39788357
DOI: 10.1016/j.cbpc.2025.110121

Abstract

The intricate interaction among host, pathogen, and environment significantly influences aquatic health, yet the influence of hypoxic stress combined with bacterial infection on host response is understudied. Circular RNAs with stable closed-loop structures have emerged as important regulators in immunity, yet remain ill-defined in fish. In this study, we systematically explored the circRNA response in yellow catfish subjected to combined hypoxia-bacterial infection (HB) stress. Following HB stress, H&E and TUNEL staining identified heightened hepatocyte apoptosis, intracellular vacuolation, and inflammatory tissue damage. RT-qPCR elucidated that differentially expressed genes stimulated by HB synergistically enhanced apoptosis and inflammatory responses. Importantly, we systematically evaluated differentially expressed circRNAs (DEcirs) in yellow catfish under hypoxia with and without Aeromonas veronii infection and identified a novel HB-specific DEcir, designated as circArid4b, whose parental gene Arid4b is highly associated with apoptosis. Experiments confirmed the circular structure of circArid4b and revealed that under HB stimulation, specific knockdown of circArid4b inhibited the expression of Arid4b, while concurrent alterations in multiple apoptosis- and inflammation-related genes synergistically indicated the promotion of apoptotic and inflammatory pathways. Notably, the downregulation of circArid4b expression significantly reduced the susceptibility to bacterial infection in yellow catfish during hypoxia. These results suggest that HB-induced suppression of circArid4b promotes cell apoptosis and inflammation by inhibiting its parental gene and thereby facilitating resistance to bacterial infection during hypoxia. Our study enriches the understanding of fish circRNA mechanisms and offers novel preventive and control strategies for bacterial infections in fish under hypoxic environments.

Keywords: Antibacterial response; Apoptosis; CircRNA; Hypoxia; Pelteobagrus fulvidraco.