Mmu_Circ_0000790 Participates in the Progression of Hypoxic Pulmonary Hypertension by Increasing FOXC1 Through Sponging microRNA-374c

Abstract

Background: Circular RNAs (circRNAs) composed of exonic sequence have been described in a small number of genes, but species possess no known function. To delineate the universe of circRNAs, we performed this study to investigate the effects of mmu_circ_0000790 on the proliferation, apoptosis and migration of pulmonary artery smooth muscle cells in hypoxic pulmonary hypertension (HPH-PASMCs) by regulating the expression of FOXC1 by sponging microRNA-374c (miR-374c). Methods: Mice model of HPH and mouse HPH-PASMCs model were established to detect the expression of mmu_circ_0000790. A series of experiments were performed to elucidate the relationships among mmu_circ_0000790, miR-374c and FOXC1 in HPH. Through gain- and loss-of function approaches, the potential functions of mmu_circ_0000790, miR-374c and FOXC1 in biological characteristics of PASMCs in HPH mice were investigated. Except that, the pathway that was potentially important in HPH was also explored. Results: mmu_circ_0000790 was determined to be highly expressed in pulmonary vascular tissues and HPH-PASMCs. Besides, mmu_circ_0000790 regulated the expression of FOXC1 through sponging of miR-374c. Downregulated mmu_circ_0000790 and FOXC1 along with upregulated miR-374c inhibited proliferation while inducing apoptosis of HPH-PASMCs. Furthermore, mmu_circ_0000790 and miR-374c played an important role in pulmonary vascular remodeling in mice with HPH by regulating the role of FOXC1 in the NOTCH pathway. Conclusion: Collectively, this study suggests that mmu_circ_0000790 regulates the expression of FOXC1 through sponging miR-374c together with regulating the biological effects of the NOTCH pathway, thus affecting the biological characteristics of HPH-PASMCs. circRNA-miRNA network plays an important role for the diagnosis and treatment of HPH. Funding: None. Declaration of Interest: The authors have no competing interests to declare. Ethical Approval: This experiment was approved by the Animal Ethics Committee of Animal Ethics Committee of The Third Affiliated Hospital of Qiqihar Medical University.. All animal experiments in this study were in accordance with the principles of management and use of local laboratory animals, and followed the National Laboratory for the Management and Use of Laboratory Animals issued by the National Institutes of Health.