LncRNA MEG3 alleviates PFOS induced placental cell growth inhibition through its derived miR-770 targeting PTX3

Environ Pollut. 2022 Jan 15:293:118542. doi: 10.1016/j.envpol.2021.118542. Epub 2021 Nov 18.

Abstract

Perfluorooctane sulfonic acid (PFOS) is a persistent environmental pollutant. Exposure to PFOS has been associated with abnormal fetal development. The long non-coding RNA (lncRNA) has been showed to play a role in fetal growth restriction (FGR), preeclampsia (PE) and other pregnancy complications. Whether the lncRNA contributes to PFOS-induced toxicity in the placenta remains unknown. In this study, we investigated the function of lncRNA MEG3 and its derived miR-770 in PFOS-induced placental toxicity. Pregnant mice received gavage administration of different concentrations of PFOS (0.5, 2.5, and 12.5 mg/kg/day) from GD0 to GD17, and HTR-8/SVneo cells were treated with PFOS in the concentrations of 0, 10-1, 1, 10 μM. We found that expression levels of miR-770 and its host gene MEG3 were reduced in mice placentas and HTR-8/SVneo cells with exposure of PFOS. A significant hypermethylation was observed at MEG3 promoter in placentas of mice gestational-treated with PFOS. We also confirmed that MEG3 and miR-770 overexpression alleviated the cell growth inhibition induced by PFOS. Furthermore, PTX3 (Pentraxin 3) was identified as the direct target of miR-770 and it was enhanced after PFOS exposure. In summary, our results suggested that MEG3 alleviate PFOS-induced placental cell inhibition through MEG3/miR-770/PTX3 axis.

Keywords: Cell growth; PTX3; Perfluorooctane sulfonic acid; Placenta; lncRNA MEG3; miR-770.

MeSH terms

  • Alkanesulfonic Acids* / toxicity
  • Animals
  • C-Reactive Protein
  • Female
  • Fluorocarbons* / toxicity
  • Mice
  • MicroRNAs* / genetics
  • Nerve Tissue Proteins
  • Placenta
  • Pregnancy
  • RNA, Long Noncoding* / genetics

Substances

  • Alkanesulfonic Acids
  • Fluorocarbons
  • MEG3 non-coding RNA, mouse
  • MIRN770 microRNA, mouse
  • MicroRNAs
  • Nerve Tissue Proteins
  • RNA, Long Noncoding
  • neuronal pentraxin
  • C-Reactive Protein
  • perfluorooctane sulfonic acid