Combined application of whole transcriptome sequencing and ceRNA theory: lncRNA LOC110519952 participates in glucose transport under hypoxia stress in rainbow trout (Oncorhynchus mykiss) by regulating novel-m0023-5p/glut1a axis
Hypoxia is a tricky and unavoidable environmental stressor for aquaculture with ongoing ecological deterioration and increasing stocking density, resulting in serious economic losses. Rainbow trout (Oncorhynchus mykiss), a commercially important fish species worldwide, exhibits extraordinarily poor tolerance to hypoxia; however, the regulatory mechanisms under hypoxia stress have not been elucidated. In this study, rainbow trout were separately subjected to moderate (Tm12L) and acute hypoxia for 12 h (Ts12L) and 12 h reoxygenation to investigate the changes of histology, biochemical parameters and transcriptomes (mRNA, miRNA and lncRNA) in liver, and interactions between LOC110519952-novel-m0023-5p-glut1a were further verified. The results showed that acute hypoxia resulted in more severe liver oxidative injury than moderate hypoxia, and anaerobic metabolism and lipid and protein metabolism were enhanced to some extent, especially in Ts12L. We also found that innate immune response was strengthened in Tm12L, while it was inhibited in Ts12L. In addition, dozens of hypoxia-related ceRNA networks derived from 1824 differentially expressed (DE) mRNAs, 427 DEmiRNAs and 545 DElncRNAs were identified, including LOC110519952-novel-m0023-5p-glut1a, LOC110520012-miR-206-y-vegfaa, LOC118965299-novel-m0179-3p-epoa and MSTRG.7382.2-miR-184-y-hmox. Further studies validated that LOC110519952 acted as a ceRNA that can positively regulate glut1a expression by adsorbing novel-m0023-5p. Overexpression of novel-m0023-5p could promote liver cell viability and proliferation, and introduction of LOC110519952 attenuated the effects.  The findings contribute to deepen our understanding of the adaptive mechanisms used by rainbow trout in response to hypoxia stress, and provide valuable information for hypoxia-tolerant varieties breeding. Overall design: In this study, rainbow trout were separately subjected to moderate (Tm12L) and acute hypoxia for 12 h (Ts12L) and 12 h reoxygenation to investigate the changes of histology, biochemical parameters and transcriptomes (mRNA, miRNA and lncRNA) in liver, and interactions between LOC110519952-novel-m0023-5p-glut1a were further verified.