• Cell. Physiol. Biochem. · Jan 2017

    Long Non-Coding RNA MEG3 Downregulation Triggers Human Pulmonary Artery Smooth Muscle Cell Proliferation and Migration via the p53 Signaling Pathway.

    • Zengxian Sun, Xiaowei Nie, Shuyang Sun, Shumin Dong, Chunluan Yuan, Yanli Li, Bingxin Xiao, Dong Jie, and Yun Liu.
    • Department of Pharmacy, The First People's Hospital of Lianyungang, Lianyungang, China.
    • Cell. Physiol. Biochem. 2017 Jan 1; 42 (6): 2569-2581.

    Background/AimsIncreasing evidence has demonstrated a significant role of long non-coding RNAs (lncRNAs) in diverse biological processes, and many of which are likely to have functional roles in vascular remodeling. However, their functions in pulmonary arterial hypertension (PAH) remain largely unknown. Pulmonary vascular remodeling is an important pathological feature of PAH, leading to increased vascular resistance and reduced compliance. Pulmonary artery smooth muscle cells (PASMCs) dysfunction is involved in vascular remodeling. Long noncoding RNAs are potential regulators of PASMCs function. Herein, we determined whether long noncoding RNA-maternally expressed gene 3 (MEG3) was involved in PAH-related vascular remodeling.MethodsThe arterial wall thickness was examined by hematoxylin and eosin (H&E) staining in distal pulmonary arteries (PAs) isolated from lungs of healthy volunteers and PAH patients. The expression level of MEG3 was analyzed by qPCR. The effects of MEG3 on human PASMCs were assessed by cell counting Kit-8 assay, BrdU incorporation assay, flow cytometry, scratch-wound assay, immunofluorescence, and western blotting in human PASMCs.ResultsWe revealed that the expression of MEG3 was significantly downregulated in lung and PAs of patients with PAH. MEG3 knockdown affected PASMCs proliferation and migration in vitro. Moreover, inhibition of MEG3 regulated the cell cycle progression and made more smooth muscle cells from the G0/G1 phase to the G2/M+S phase and the process could stimulate the expression of PCNA, Cyclin A and Cyclin E. In addition, we found that the p53 pathway was involved in MEG3-induced smooth muscle cell proliferation.ConclusionsThis study identified MEG3 as a critical regulator in PAH and demonstrated the potential of gene therapy and drug development for treating PAH.© 2017 The Author(s). Published by S. Karger AG, Basel.

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