LncRNA AOC4P recruits TRAF6 to regulate EZH2 ubiquitination and participates in trophoblast glycolysis and M2 macrophage polarization which is associated with recurrent spontaneous abortion
LncRNA AOC4P recruits TRAF6 to regulate EZH2 ubiquitination and participates in trophoblast glycolysis and M2 macrophage polarization which is associated with recurrent spontaneous abortion
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LncRNA AOC4P募集TRAF6调节EZH2泛素化并参与滋养细胞糖酵解和M2巨噬细胞极化，这与复发性自然流产相关
DOI：
10.1016/j.intimp.2023.111201
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发表时间：
2023-11-09
影响因子：
5.6
通讯作者：
Yang，Jing
中科院分区：
文献类型：
--
作者：
Wu，Shujuan;Han，Lu;Yang，Jing
在胚胎着床过程中，滋养细胞依靠糖酵解产生的大量能量来快速生长和侵袭。滋养细胞代谢紊乱可导致复发性自然流产（RSA）。妊娠早期滋养细胞糖酵解产生的乳酸可促进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，在RSA患者的绒毛中，胺氧化酶含铜4假基因（AOC4P）异常升高。抑制滋养层细胞糖酵解，从而抑制M2巨噬细胞的极化。进一步研究表明，AOC4P联合肿瘤坏死因子受体相关因子6 （tumor necrosis factor receptor-associated factor 6, TRAF6）上调TRAF6的表达。TRAF6作为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AOC4P在母胎界面的重要作用提供了新的见解。
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.