LncRNA AOC4P 招募 TRAF6 来调节 EZH2 泛素化，并参与与复发性自然流产相关的滋养层糖酵解和 M2 巨噬细胞极化。
LncRNA AOC4P recruits TRAF6 to regulate EZH2 ubiquitination and participates in trophoblast glycolysis and M2 macrophage polarization which is associated with recurrent spontaneous abortion.
发表日期：2023 Nov 09
作者：
Shujuan Wu, Lu Han, Mengqi Zhou, Xing Li, Lingbo Luo, Zehao Wang, Sisi Yan, Faminzi Li, Jiao Chen, Jing Yang
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要：
在胚胎植入过程中，滋养层细胞依靠糖酵解产生的大量能量来快速生长和侵袭。滋养层代谢紊乱可能导致复发性自然流产（RSA）。妊娠早期滋养层细胞糖酵解产生的乳酸可以促进M2巨噬细胞的极化，维持母胎界面的抗炎环境。我们的研究发现，RSA患者绒毛中胺氧化酶含铜4假基因（AOC4P）异常升高。它抑制滋养层细胞的糖酵解，从而阻碍 M2 巨噬细胞的极化。进一步研究表明，AOC4P与肿瘤坏死因子受体相关因子6（TRAF6）结合，上调TRAF6表达。 TRAF6 充当 E3 泛素连接酶，促进 zeste 同源物 2 (EZH2) 的泛素化和降解。这些结果为了解 AOC4P 在母胎界面中发挥的重要作用提供了新的见解。版权所有 © 2023 Elsevier B.V. 保留所有权利。
During embryo implantation, trophoblast cells rely on large amounts of energy produced by glycolysis for their rapid growth and invasion. The disorder of trophoblast metabolism may lead to recurrent spontaneous abortion (RSA). Lactate, which is produced by the glycolysis of trophoblast cells during early pregnancy, can promote the polarization of M2 macrophages and maintain an anti-inflammatory environment at the maternal-fetal interface. Our study found that amine oxidase copper-containing 4 pseudogene (AOC4P) was abnormally increased in villi from RSA patients. It inhibited the glycolysis of trophoblast cells and thus hindered the polarization of M2 macrophages. Further studies showed that AOC4P combines with tumor necrosis factor receptor-associated factor 6 (TRAF6) to upregulate TRAF6 expression. TRAF6 acted as an E3 ubiquitin ligase to promote ubiquitination and degradation of zeste homolog 2 (EZH2). These results provided new insights into the important role played by AOC4P at the maternal-fetal interface.Copyright © 2023 Elsevier B.V. All rights reserved.