Long noncoding RNA Hoxaas3 contributes to hypoxia-induced pulmonary artery smooth muscle cell proliferation

Abstract Aims Long noncoding RNAs (lncRNAs) are involved in the regulation of vascular smooth muscle cells and cardiovascular pathology. However, the contribution of lncRNAs to pulmonary hypertension (PH) remains largely unknown. The over-proliferation of pulmonary artery smooth muscle cells (PASMCs) causes pulmonary arterial smooth muscle hypertrophy and stenosis of the pulmonary vascular lumen, resulting in PH. Here, we investigated the biological role of a novel lncRNA, Hoxa cluster antisense RNA 3 (Hoxaas3), in the regulation of cell proliferation in PH. Methods and results Hoxaas3 was up-regulated in the lung vasculature of hypoxic mice and in PASMCs under hypoxic conditions. Histone H3 Lysine 9 acetylation of Hoxaas3 promoted gene expression. Moreover, high expression of Hoxaas3 was associated with cell proliferation and modulated cell cycle distribution by up-regulating Homeobox a3 at the mRNA and protein levels. Conclusion This study defined the role and mechanism of action of Hoxaas3 in the regulation of cell proliferation in PH, which should facilitate the development of new therapeutic strategies for the treatment of this disease.