Dysfunction of pseudogene PGK1P2 is involved in preeclampsia by acting as a competing endogenous RNA of PGK1

Abstract

Objectives: Normal decidualization is essential for normal pregnancy and abnormal decidualization is thought to cause preeclampsia (PE). Phosphoglycerate kinase 1 (PGK1) is an enzyme involved in the glycolytic pathway which is the main metabolism process decidual cells exhibit. Phosphoglycerate kinase 1, pseudogene 2 (PGK1P2), which is also a long non-coding RNA (lncRNA), has a high sequence similarity to PGK1 and therefore acquires an ability for sequence-specific regulation.

Methodology: The expression of PGK1 and PGK1P2 in human decidua, as well as their relationship and functions during decidualization was investigated using in vitro cultured human endometrial stromal cell lines (hESCs) and primary ESCs by real-time PCR, immunohistochemistry, western blotting, siRNA techniques and miRNA inhibitor or mimic transfection.

Results: The levels of PGK1 and PGK1P2 mRNA and PGK1 protein in severe preeclamptic decidua were lower than those in normal pregnant controls. PGK1 and PGK1P2 mRNAs were both induced after in vitro decidualization and their deficiency caused impaired decidualization in turn. We also found PGK1P2 acted as a competing endogenous RNA (ceRNA) to regulate PGK1 expression through miR-330-5p.

Conclusions: We proved that PGK1 and PGK1P2 are a pair of ceRNAs against miR-330-5p and they play a vital role in human decidualization by regulating angiogenesis and glycolysis metabolism. The deficiency of PGK1 and PGK1P2 in the decidua jeopardizes the decidualization process and subsequently might lead to the occurrence of PE. These findings may help in promoting novel predictive, diagnostic and prognostic biomarkers of PE in future.

Keywords: Competing endogenous RNA; LncRNA; PGK1; PGK1P2; Preeclampsia; miRNA-330-5p.