Circular RNA circ_0032962 promotes trophoblast cell progression as ceRNA to target PBX3 via sponging miR-326 in preeclampsia

Reprod Biol. 2021 Dec;21(4):100571. doi: 10.1016/j.repbio.2021.100571. Epub 2021 Nov 3.

Abstract

Preeclampsia (PE) is the leading cause of maternal deaths in primipara. It is mainly characterized by defect migration and invasion of trophoblast cells. Circular RNAs (circRNAs) have been widely reported to be associated with PE progression. This study is designed to explore the role and mechanism of circ_0032962 on trophoblast cell behavior. Circ_0032962, microRNA-326 (miR-326), and Pre-B-cell leukemia homeobox 3 (PBX3) levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation ability, migration, and invasion were measured by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), Colony formation, wound healing, and transwell assays. Protein levels of E-cadherin, Vimentin, N-cadherin, and PBX3 were examined by western blot assay. The binding relationship between miR-326 and circ_0032962 or PBX3 was predicted by circular RNA Interactome or Starbase and then verified by a dual-luciferase reporter assay. Circ_0032962 and PBX3 levels were declined in placenta tissues from preeclampsia patients, and miR-326 was elevated. Apart from that, circ_0032962 knockdown could suppress cell proliferation ability, migration, invasion, and epithelial-mesenchymal transition (EMT) in trophoblast cells. Mechanically, circ_0032962 could affect PBX3 expression through sponging miR-326. Circ_0032962 could contribute to trophoblast cell growth ability and metastasis partly by regulating the miR-326/PBX3 axis, providing a novel insight into the pathogenesis and treatment of PE.

Keywords: PBX3; Preeclampsia; Trophoblast cells; circ_0032962; miR-326.

MeSH terms

  • Case-Control Studies
  • Cell Line
  • Female
  • Homeodomain Proteins / metabolism*
  • Humans
  • MicroRNAs / metabolism*
  • Pre-Eclampsia / etiology
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Circular / metabolism*
  • Trophoblasts / physiology*

Substances

  • Homeodomain Proteins
  • MIRN326 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Circular
  • proto-oncogene protein Pbx3