Dysregulated Pseudogene HK2P1 May Contribute to Preeclampsia as a Competing Endogenous RNA for Hexokinase 2 by Impairing Decidualization

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Abstract

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 HK2P1 (hexokinase 2 pseudogene 1) and its cognate gene HK2 (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 HK2P1 and HK2 during decidualization. HK2 is the crucial enzyme involved in glycolysis. The HK2P1 and HK2 genes are homologous to each other. The results demonstrated that HK2P1, like HK2, stimulated the glucose uptake and lactate production of human endometrial stromal cells. In addition, HK2P1 and HK2 are indispensable for endometrial decidualization. Downregulated HK2P1 or HK2 inhibited human endometrial stromal cells proliferation and differentiation. Furthermore, there was a significant positive correlation between the expression of HK2P1 and HK2, and HK2P1 regulated the HK2 expression via competition for the shared miR-6887-3p. Taken together, our results indicated that the reduced expression of HK2P1 and HK2 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.

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