Overexpression of Long Noncoding RNA Uc.187 Induces Preeclampsia-Like Symptoms in Pregnancy Rats

Abstract

Background: As a serious pregnancy-specific condition, preeclampsia (PE) is a serious pregnancy-specific condition characterized by insufficient trophoblastic invasion and shallow placental implantation. Long noncoding RNA uc.187, which is transcribed from an ultra-conserved region is highly expressed in the placental tissue of patients with PE, is associated with abnormal trophoblast invasion. Therefore, we aimed to further characterize the relationship between uc.187 and PE through in vitro experimental studies to find new targets to treat PE.

Methods: In this study, we constructed PE rat models induced by lipopolysaccharide, experimented with overexpressing uc.187 and performed experiments using HTR-8/SVneo cells.

Results: We found uc.187 was elevated in the placenta of PE rats. By injecting pregnant rats with a lentivirus containing the lncRNA uc.187, we successfully triggered maternal hypertension along with a series of symptoms similar to PE in humans. In vitro experiments demonstrated that high levels of uc.187 lead to decreased trophoblast invasion. In addition, our results revealed that uc.187 had high expression in PE and fetal growth restricted cells, but low expression in placental site trophoblastic tumors compared with the control groups. Results of western blot and cell immunofluorescence indicated that the aberrant biological behavior of HTR-8/SVneo cells were related to the distribution of β-catenin in the cytoplasm and nucleus.

Conclusions: Taken together, our study revealed that uc.187 was negatively correlated to trophoblastic cell invasion, and overexpression of uc.187 could induce PE-like symptoms in a pregnant rat model by affecting the distribution of β-catenin in the cytoplasm and nucleus.

Keywords: blood pressure; hypertension; invasion; long noncoding RNA; preeclampsia; rat model; uc.187.