Elevated levels of hypoxia‐inducible microRNA‐210 in pre‐eclampsia: new insights into molecular mechanisms for the disease

Journal of Cellular and Molecular Medicine

Yi Zhang³  Mingyu Fei³  Geng Xue³  Qi Zhou³  Yin Jia³  Li Li²  Hong Xin¹ 

[1] Department of Obstetrics and Gynecology, Second Hospital of Hebei Medical University, Shijiazhuang, China;Department of Obstetrics and Gynecology, First Affiliated Hospital of Anhui Medical University, Hefei, China;Department of Medical Genetics, Second Military Medical University, Shanghai, China

关键词: pre‐eclampsia;    hypoxia;    microRNA;    trophoblast cell;    transcriptional regulation;   

DOI  :  10.1111/j.1582-4934.2011.01291.x

来源: Wiley

【 摘 要 】

Abstract

Pre-eclampsia is a leading cause of maternal and foetal morbidity and mortality worldwide. Insufficient uteroplacental oxygenation is believed to be responsible for the disease. However, what molecular events involve in hypoxic responses and how they affect placental development remain unclear. Recently, miRNAs have emerged as a new class of molecules in response to hypoxia. We show here that the expression of microRNA-210 (mir-210) is up-regulated in patients with pre-eclampsia, as well as in trophoblast cells cultured under hypoxic conditions. Ectopic expression of mir-210 inhibited the migration and invasion capability of trophoblast cells. Ephrin-A3 and Homeobox-A9, which related with cell migration and vascular remodelling, were then experimentally validated as the functional targets of mir-210 both in vivo and in vitro. Using luciferase reporter, chromatin immunoprecipitation (ChIP) and small interfering RNA (siRNA) experiments, we finally identified a new transcriptional mechanism that the overexpression of mir-210 under hypoxia was regulated by NF-κB transcriptional factor p50, apart from the well-known HIF 1α. Taken together, our study implicates an important role for mir-210 in the molecular mechanism of pre-eclampsia.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd