Dysregulated Pseudogene May Contribute to Preeclampsia as a Competing Endogenous RNA for Hexokinase 2 by Impairing Decidualization.

Preeclampsia is a pregnancy-specific hypertensive disorder, which seriously undermines the health of maternity and fetus. However, its cause and pathogenesis remain elusive. Flawed decidualization is considered to be related to preeclampsia. Increasing evidence indicates that long noncoding RNAs are correlated with a variety of diseases, including preeclampsia. In this study, we verified the expression of long noncoding RNA (hexokinase 2 pseudogene 1) and its cognate gene (hexokinase 2), which were found by our previous RNA-sequencing analysis in the decidua of severe preeclampsia patients and matched control subjects. Besides that, we also investigated the function and the mechanism of and during decidualization. HK2 is the crucial enzyme involved in glycolysis. The and genes are homologous to each other. The results demonstrated that , like , stimulated the glucose uptake and lactate production of human endometrial stromal cells. In addition, and are indispensable for endometrial decidualization. Downregulated or inhibited human endometrial stromal cells proliferation and differentiation. Furthermore, there was a significant positive correlation between the expression of and , and regulated the expression via competition for the shared miR-6887-3p. Taken together, our results indicated that the reduced expression of and may have contributed to the occurrence and development of preeclampsia by suppressing glycolysis and impairing decidualization. Our study would be helpful to understand the pathogenesis and the regulatory network of preeclampsia.