LINC00473 downregulation facilitates trophoblast cell migration and invasion via the miR-15a-5p/LITAF axis in pre-eclampsia

Environ Toxicol. 2021 Aug;36(8):1618-1627. doi: 10.1002/tox.23157. Epub 2021 Apr 28.

Abstract

More and more evidence has identified that long non-coding RNAs (lncRNAs) are involved in various biological process of numerous diseases. It has been reported that long intergenic non-protein coding RNA 473 (LINC00473) was associated with pre-eclampsia (PE) development. However, role and molecular mechanism of LINC00473 in PE remains elusive. Therefore, we designed this research to figure out the specific biological function of LINC00473 in trophoblasts. Firstly, we testified expressions of LINC00473 in trophoblasts of PE with RT-qPCR analysis. Then, to probe biological function of LINC00473 in trophoblasts of PE, CCK-8 assay, trans-well assays and western blot analysis were conducted in Wish and JAR cells. As for verifying interaction of microRNA-15a-5p (miR-15a-5p) and LINC00473 or lipopolysaccharide induced TNF factor (LITAF), RNA pull-down and luciferase reporter assays were carried out. Finally, rescue experiments were conducted to probe regulatory pattern of the LINC00473/miR-15a-5p/LITAF axis in trophoblasts of PE. As a result, LINC00473 presented a significant upregulation in trophoblasts of PE. Moreover, LINC00473 knockdown induced trophoblast viability, migration, invasion, and epithelial-to-mesenchymal transition (EMT) in trophoblasts. Additionally, miR-15a-5p interacted with LINC00473 and miR-15a-5p was negatively regulated by LINC00473 in trophoblasts. Simultaneously, miR-15a-5p negatively modulated LITAF in trophoblasts. Moreover, LITAF overexpression or miR-15a-5p downregulation reversed the promotive impact of silenced LINC00473 on trophoblast viability, migration, invasion and EMT. In conclusion, LINC00473 regulated migration and invasion in trophoblasts via the miR-15a-5p/LITAF axis. Our study may provide a novel insight for clinical treatment of PE.

Keywords: LINC00473; LITAF; miR-15a-5p; pre-eclampsia.

MeSH terms

  • Cell Movement
  • Down-Regulation
  • Female
  • Humans
  • Lipopolysaccharides
  • MicroRNAs*
  • Nuclear Proteins
  • Pre-Eclampsia*
  • Pregnancy
  • RNA, Long Noncoding
  • Transcription Factors
  • Trophoblasts

Substances

  • LINC00473 RNA, human
  • LITAF protein, human
  • Lipopolysaccharides
  • MIRN15 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • Transcription Factors