Interference with lncRNA NEAT1 promotes the proliferation, migration, and invasion of trophoblasts by upregulating miR-411-5p and inhibiting PTEN expression

Immunopharmacol Immunotoxicol. 2021 Jun;43(3):334-342. doi: 10.1080/08923973.2021.1910834. Epub 2021 Apr 20.

Abstract

Background: Preeclampsia (PE) is an idiopathic hypertensive disorder of pregnancy, which is related to abnormal placental villi development. Our previous study has found that lncRNA NEAT1 promotes apoptosis of trophoblasts, but the role of NEAT1 in proliferation, migration, and invasion is still unclear. This study explores the role of NEAT1 in proliferation, migration, and invasion of trophoblasts.Methods: NEAT1 and miR-411-5p levels were detected by quantitative real-time PCR. Colony formation assay detected cell proliferation and transwell assay detected cell migration and invasion. Dual-luciferase reporter assay detected the binding between NEAT1 and miR-411-5p as well as the binding between miR-411-5p and PTEN. RNA pull-down assay detected the combination between NEAT1 and miR-411-5p.Result: NEAT1 was increased and miR-411-5p was reduced in PE patients and human trophoblasts (HTR8/SVneo cells) that were induced with H2O2. Interference with NEAT1 promoted cell proliferation, migration, and invasion, and the miR-411-5p inhibitor reversed the effect of siRNA-NEAT1. The expression of PTEN was promoted in PE patients and HTR8/SVneo cells that were induced with H2O2, while the miR-411-5p mimic inhibited PTEN expression, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic. Besides, under H2O2 induction, the miR-411-5p mimic promoted cell proliferation, migration, and invasion, and the plasmid-mediated PTEN overexpression reversed the effect of the miR-411-5p mimic.Conclusion: Interference with lncRNA NEAT1 promoted the proliferation, migration, and invasion of trophoblasts and alleviated the development of PE, which was partly mediated by upregulating miR-411-5p and inhibiting PTEN expression.

Keywords: LncRNA NEAT1; PTEN; Preeclampsia; Trophoblast; miR-411-5p.

Publication types

  • Video-Audio Media

MeSH terms

  • Cell Line
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Developmental*
  • Humans
  • MicroRNAs / biosynthesis*
  • PTEN Phosphohydrolase / biosynthesis*
  • Pregnancy
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Trophoblasts / metabolism*
  • Up-Regulation*

Substances

  • MIRN411 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • PTEN Phosphohydrolase
  • PTEN protein, human