RT Journal Article
SR Electronic
T1 Long Noncoding RNA- Maternally Expressed Gene 3 Contributes to Hypoxic Pulmonary Hypertension
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 243063
DO 10.1101/243063
A1 Yan Xing
A1 Xiaodong Zheng
A1 Yao Fu
A1 Jing Qi
A1 Minghui Li
A1 Haisheng Peng
A1 Shuang Wang
A1 Shuzhen Li
A1 Daling Zhu
YR 2018
UL http://biorxiv.org/content/early/2018/01/04/243063.abstract
AB The expression and function of long noncoding RNAs (lncRNAs) in the development of hypoxic pulmonary hypertension, especially in the proliferation of pulmonary artery smooth muscle cells (PASMCs) are largely unknown. Here, we characterized the expression of lncRNA-maternally expressed gene 3 (lncRNA-MEG3) was significantly increased and primarily located in the cytoplasm of PASMCs by hypoxia. LncRNA-MEG3 knockdown by lung-specific delivery of small interfering RNAs (siRNAs) significantly prevented the development of hypoxic pulmonary hypertension in vivo. Silencing of lncRNA-MEG3 by siRNAs and gapmers attenuated PASMC responses to hypoxia in vitro. Mechanically, we found that lncRNA-MEG3 acts as a molecular sponge of microRNA-328 (miR-328); upon hypoxia, lncRNA-MEG3 interacts and sequesters miR-328, leading to the upregulation of insulin-like growth factor 1 receptor (IGF1R). Additionally, higher expression of lncRNA-MEG3 and IGF1R, and lower expression of miR-328 were observed in PASMCs of iPAH patients. These data provide insight into the contribution of lncRNA-MEG3 in hypoxia pulmonary hypertension. Upregulation of lncRNA-MEG3 sequesters cytoplasmic miR-328, eventually leading to the expression of IGF1R, revealing a regulatory mechanism by lncRNAs in hypoxia-induced PASMC proliferation.