Oxygen utilization characterization of circRNA-miRNA-mRNA regulatory networks in alveolar type II epithelial cells of Tibetan pigs

Understanding the signaling pathways regulatory mechanisms of (alveolar type II epithelial) ATII cells from Tibetan pigs, which is the progenitor cells responsible for proliferating and regenerating (alveolar type I epithelial) ATI and ATII cells, and beneficial for exploring method of prevent and repair cellular damage during hypoxia. In this study, we simulated the hypoxia environment (2% O2) for culturing ATII cells of Tibetan pigs and Landrace pigs, and constructed normal oxygen concentration (21% O2) as control group to integrate analysis circRNA-miRNA-mRNA regulatory axis by whole transcriptome. Functional enrichment assessment indicated that the source genes of DEcircRNAs were primarily engaged in cell proliferation, cellular process, and cell killing. A series of DEcircRNAs were derived from a member of the inhibitors of apoptosis proteins and lead one of the key autonomous effects as a modulator of cell repair of Tibetan pigs under hypoxia. In addition, ceRNA network functional interactions was constructed, including novel_circ_000898-ssc-miR-199a-5p-CAV1 and novel_circ_000898- ssc-miR-378-BMP2 base on the center gene of ssc-miR-199a-5p and ssc-miR-378, which may regulate many miRNAs and mRNAs mediated ER stress-induced apoptosis and inflammation, and attenuates hypoxia-induced injury of ATII cells under hypoxia conditions. These results broaden our acknowledging of circRNA, miRNA, and mRNAs associated with hypoxia-induce and provide new insights into the hypoxia response of ATII cells in Tibetan pigs.