Pseudogene fms-related tyrosine kinase 1 pseudogene 1 (FLT1P1) cooperates with RNA binding protein dyskeratosis congenita 1 (DKC1) to restrain trophoblast cell proliferation and angiogenesis by targeting fms-related tyrosine kinase 1 (FLT1) in preeclampsia

Bioengineered. 2021 Dec;12(1):8885-8897. doi: 10.1080/21655979.2021.1988366.

Abstract

In preeclampsia (PE), preexistent maternal endothelial dysfunction leads to impaired placentation and vascular maladaptation. Long noncoding RNAs (lncRNAs) have been shown to participate in the placentation process. LncRNA fms-related tyrosine kinase 1 pseudogene 1 (FLT1P1) was previously reported to be upregulated in PE. In this study, we verified the effect of FLT1P1 and its cognate gene FLT1 on trophoblast cell proliferation and angiogenesis by using Cell Counting Kit-8 (CCK-8) assay, tube formation assay, and western blot analysis. Their binding to RNA binding protein dyskeratosis congenita 1 (DKC1) was validated by conducting RNA immunoprecipitation (RIP) and RNA pulldown assays. In this study, knockdown of FLT1P1 or FLT1 was found to promote cell proliferation and angiogenesis in trophoblasts. In addition, FLT1P1 recruited DKC1 to stabilize FLT1. Importantly, silencing FLT1P1 or DKC1 decreased the stability of FLT1. Rescue assays revealed that FLT1 overexpression reversed the effect of silenced FLT1P1. Overall, FLT1P1 cooperates with DKC1 to restrain trophoblast cell proliferation and angiogenesis by targeting FLT1.

Keywords: DKC1; FLT1; FLT1P1; preeclampsia.

MeSH terms

  • Apoptosis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation*
  • Humans
  • MicroRNAs / genetics
  • Neovascularization, Pathologic*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / pathology*
  • Pregnancy
  • Pseudogenes*
  • RNA, Long Noncoding / genetics
  • Trophoblasts / metabolism
  • Trophoblasts / pathology*
  • Vascular Endothelial Growth Factor Receptor-1 / genetics
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism*

Substances

  • Cell Cycle Proteins
  • DKC1 protein, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1

Grants and funding

The author(s) reported that there is no funding associated with the work featured in this article.