• Yuhan Qin, Boqian Zhu, Linqing Li, Dong Wang, Yong Qiao, Bo Liu, Erfei Luo, Jiantong Hou, Gaoliang Yan, and Chengchun Tang.
• Medical School of Southeast University, Nanjing, Jiangsu, China.
• Shock. 2021 Feb 1; 55 (2): 244-255.

BackgroundHypoxic pulmonary hypertension (HPH) is a devastating and incurable disease characterized by pulmonary vascular remodeling, resulting in right heart failure and even death. Accumulated evidence has confirmed long coding RNAs (lncRNAs) are involved in hypoxia-induced pulmonary vascular remodeling in HPH. The exact mechanism of lncRNA in hypoxic pulmonary hypertension remains unclear.MethodsMicroarray analysis was applied to investigate the profiles of lncRNA expression in pulmonary artery smooth muscle cells (PASMCs) cultured under hypoxia and normoxia condition. qRT-PCR was performed for the expression of lncRNAs, miRNA, and mRNAs, western blot analysis was employed for the detection of the expression of proteins. CCK-8 and transwell chamber assay were applied for the assessment of PASMC proliferation and migration, respectively. Besides, flow cytometry was performed for assessments of cell cycle progression. The binding between AC068039.4 and miR-26a-5p, miR-26a-5p, and TRPC6 3'UTR was detected by dual luciferase reporter assay.ResultsA total of 1,211 lncRNAs (698 up-regulated and 513 down-regulated) were differently expressed in hypoxia-induced PASMCs. Consistent with microarray analysis, quantitative PCR verified that AC068039.4 was obviously up-regulated in hypoxia-induced PASMCs. Knocking down AC068039.4 alleviated proliferation and migration of PASMCs and regulated cell cycle progression through inhibiting cells entering the G0/G1 cell cycle phase. Further experiment indicated AC068039.4 promoted hypoxic PASMCs proliferation via sponging miR-26-5p. In addition, transient receptor potential canonical 6 (TRPC6) was confirmed to be a target gene of miR-26a-5p.ConclusionIn conclusion, downregulation of lncRNA AC068039.4 inhibited pulmonary vascular remodeling through AC068039.4/miR-26a-5p/TRPC6 axis, providing new therapeutic insights for the treatment of HPH.Copyright © 2020 by the Shock Society.

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