Enhanced HOXA10 sumoylation inhibits embryo implantation in women with recurrent implantation failure.
Ruiwei JiangLijun DingJianjun ZhouChenyang HuangQun ZhangYue JiangJingyu LiuQiang YanXin ZhenJianxin SunGuijun YanHaixiang SunPublished in: Cell death discovery (2017)
HOXA10 has emerged as an important molecular marker of endometrial receptivity. Recurrent implantation failure (RIF) after in vitro fertilization-embryo transplantation (IVF-ET) treatment is associated with impaired endometrial receptivity, but the exact underlying mechanism of this phenomenon remains elusive. Here we found that HOXA10 was modified by small ubiquitin like-modifier 1 (SUMO1) at the evolutionarily conserved lysine 164 residue. Sumoylation inhibited HOXA10 protein stability and transcriptional activity without affecting its subcellular localization. SUMO1-modified HOXA10 expression was decreased in estradiol- and progesterone-treated Ishikawa cells. Sumoylation inhibited the accelerant role of HOXA10 in BeWo spheroid and mouse embryo attachment to Ishikawa cells. Importantly, aberrantly high SUMO1-HOXA10 expression was detected in mid-secretory endometria of women with RIF compared with that of the control fertile women. Together, our results suggest that HOXA10 sumoylation impairs the process of embryo implantation in vitro and takes part in the development of RIF.
Keyphrases
- long non coding rna
- long noncoding rna
- poor prognosis
- pregnancy outcomes
- induced apoptosis
- pulmonary tuberculosis
- transcription factor
- type diabetes
- binding protein
- cell cycle arrest
- polycystic ovary syndrome
- mesenchymal stem cells
- amino acid
- bone marrow
- adipose tissue
- oxidative stress
- cell proliferation
- insulin resistance
- cell death
- replacement therapy
- newly diagnosed
- protein protein
- density functional theory
- heat shock protein