Effect and mechanism of microRNA-515-5p in proliferation and apoptosis of trophoblast cells in preeclampsia via manipulating histone deacetylase 2

Mol Reprod Dev. 2023 Jan;90(1):59-66. doi: 10.1002/mrd.23649. Epub 2022 Dec 29.

Abstract

Preeclampsia (PE) refers to a pregnancy-specific disease that begins with the placenta. Differentially expressed microRNAs (miRs) are a feature of PE. This study tried to elicit the functional mechanism of miR-515-5p in trophoblast cell behaviors in PE. First, HTR-8/SVneo cells were transfected with miR-515-5p mimic or miR-515-5p inhibitor. Then, relative expression levels of miR-515-5p and histone deacetylase 2 (HDAC2) in HTR-8/SVneo cells were determined by reverse transcription-quantitative polymerase chain reaction. The potential binding site of miR-515-5p and HDAC2 was predicted on Targetscan and their binding relationship was verified via dual-luciferase assay. Proliferation, apoptosis, invasion, and migration of HTR-8/SVneo cells were assessed via cell counting kit-8, flow cytometry, Transwell, and wound healing assays, respectively. Protein levels of Cleaved caspase-3, Bcl-2, and Bax were determined via Western blot. Overexpressed miR-515-5p impeded proliferation and stimulated apoptosis of HTR-8/SVneo cells, and decreased levels of Cleaved caspase-3 and Bax and elevated Bcl-2, whilst opposite results were observed after miR-515-5p inhibition. miR-515-5p targeted HDAC2. Knockdown of HDAC2 annulled the promotional action of miR-515-5p inhibition on proliferative, invasive, and migratory abilities and its antiapoptotic action on HTR-8/SVneo cells. In brief, miR-515-5p affected the proliferation, apoptosis, invasion, and migration of HTR-8/SVneo cells by targeting HDAC2.

Keywords: apoptosis; histone deacetylase 2; microRNA-515-5p; preeclampsia; proliferation; trophoblast cells.

MeSH terms

  • Apoptosis / genetics
  • Caspase 3 / metabolism
  • Cell Line
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Histone Deacetylase 2 / genetics
  • Histone Deacetylase 2 / metabolism
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pre-Eclampsia* / genetics
  • Pre-Eclampsia* / metabolism
  • Pregnancy
  • Trophoblasts / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • MicroRNAs
  • Caspase 3
  • Histone Deacetylase 2
  • bcl-2-Associated X Protein
  • MIRN515 microRNA, human