Regulatory effects of circular RNA on hypoxia adaptation in chicken embryos

Abstract The Tibetan chicken, a native breed of the Tibetan plateau, is adapted to the high-altitude and hypoxic environment of the plateau. As endogenous molecules, circular RNAs (circRNAs) have been shown to play an important role in the adaptation to hypoxic environments and regulation of angiogenesis. In this study, highland Tibetan and lowland Chahua chicken eggs were incubated in a hypoxic environment and the chorionic allantoic membrane was collected for Ribo-Zero RNA sequencing. A total of 1,414 circRNAs, mostly derived from exons, were identified. Of these, 93 differentially expressed circRNAs were detected between Tibetan and Chahua chickens. Combined with the differentially expressed miRNAs and mRNAs identified in our previous study, we identified four circRNAs (circBRD1, circPRDM2, circPTPRS, and circDENND4C). These circRNAs may act as competing endogenous RNA (ceRNA) to upregulate APOA1 expression by absorbing novel_miR_589, thereby regulating angiogenesis and affecting hypoxia adaptation in chicken embryos. The regulatory circRNAs/novel_miR_589/APOA1 axis provides valuable evidence for a better understanding of the specific functions and molecular mechanisms of circRNAs in plateau hypoxia adaptation in Tibetan chickens.