Wang Yali, Tan Xiaoming, Wu Yunjiang, Cao Sipei, Lou Yueyan, Zhang Liyan, Hu Feng
Department of Respiratory Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Thoracic Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
Front Genet. 2021 Jul 12;12:673229. doi: 10.3389/fgene.2021.673229. eCollection 2021.
Currently, new strategies for the diagnosis and treatment of hypoxia-induced pulmonary hypertension (HPH) are urgently required. The unique features of circRNAs have unveiled a novel perspective for understanding the biological mechanisms underlying HPH and the possibility for innovative strategies for treatment of HPH. CircRNAs function as competing endogenous RNAs (CeRNA) to sequester miRNAs and regulate the expression of target genes. This study aimed to explore the roles of hsa_circ_0002062 on the biological behaviors of pulmonary artery smooth muscle cells (PASMCs) in hypoxic conditions. A number of assays, such as RNA-binding protein immunoprecipitation (RIP), RNA pull-down, and dual-luciferase assays were performed to evaluate the interrelationship between hsa_circ_0002062, hsa-miR-942-5P, and CDK6. The potential physiological functions of hsa_circ_0002062, hsa-miR-942-5P, and CDK6 in hypoxic PASMCs were investigated through expression modulation. Our experiments demonstrated that hsa_circ_0002062 functions as a ceRNA, acts as a sponge for hsa-miR-942-5P, and consequently activates CDK6, which further promotes pulmonary vascular remodeling. Therefore, we speculate that hsa_circ_0002062 could serve as a candidate diagnostic biomarker and potential therapeutic target for HPH.
目前，迫切需要用于诊断和治疗缺氧诱导的肺动脉高压（HPH）的新策略。环状RNA（circRNAs）的独特特性为理解HPH潜在的生物学机制以及创新治疗策略提供了新视角。circRNAs作为竞争性内源RNA（CeRNA）发挥作用，通过结合微小RNA（miRNAs）来调控靶基因的表达。本研究旨在探讨hsa_circ_0002062在低氧条件下对肺动脉平滑肌细胞（PASMCs）生物学行为的影响。通过RNA结合蛋白免疫沉淀（RIP）、RNA下拉和双荧光素酶报告基因检测等实验评估hsa_circ_0002062、hsa-miR-942-5P和细胞周期蛋白依赖性激酶6（CDK6）之间的相互关系。通过调控hsa_circ_0002062、hsa-miR-942-5P和CDK6的表达，研究它们在低氧PASMCs中的潜在生理功能。我们的实验表明，hsa_circ_0002062作为CeRNA，充当hsa-miR-942-5P的海绵，进而激活CDK6，进一步促进肺血管重塑。因此，我们推测hsa_circ_0002062可能是HPH的候选诊断生物标志物和潜在治疗靶点。
