Decreased circUBAP2 Expression Is Associated with Preeclampsia by Limiting Trophoblast Cell Proliferation and Migration

Reprod Sci. 2021 Aug;28(8):2237-2245. doi: 10.1007/s43032-020-00450-w. Epub 2021 Jan 27.

Abstract

Preeclampsia (PE) is a common obstetric disease and a major cause of maternal, newborn, and fetal death. This condition is a multisystem disorder characterized by hypertension, proteinuria, and involvement of the kidney, liver, and nervous system. It is generally believed that the placenta is the main cause of PE. circRNAs are a special class of noncoding RNAs that can form covalently closed continuous ring structures with tissue-specific conservation, and they have been reported to play a wide range of regulatory functions in various diseases, including PE. In this study, we reported a novel circUBAP2 (hsa_circ_0003496) and found that it was downregulated in placental tissues from patients with PE compared to healthy controls. After knocking down circUBAP2 in trophoblast cells, we found that cell proliferation and migration were significantly suppressed. In addition, preliminary mechanistic studies showed that circUBAP2 can sponge miR-1244, and FOXM1 was identified as a target gene for miR-1244. Cotransfection of si-circUBAP2 and a miR-1244 inhibitor partially reversed the suppressive effect induced by circUBAP2 depletion on proliferation and migration. In conclusion, the circUBAP2/miR-1244/FOXM1 axis might be a promising molecular marker for the diagnosis and treatment of PE.

Keywords: FOXM1; Placenta; Preeclampsia; circUBAP2; miR-1244.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cell Line
  • Cell Movement / physiology*
  • Cell Proliferation / physiology*
  • Female
  • Humans
  • Placenta / metabolism*
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Trophoblasts / metabolism*

Substances

  • RNA, Circular