LncRNA DLEU1 is overexpressed in premature ovarian failure and sponges miR-146b-5p to increase granulosa cell apoptosis

J Ovarian Res. 2021 Nov 5;14(1):151. doi: 10.1186/s13048-021-00905-x.

Abstract

Background: miR-146b-5p has been reported to participate in premature ovarian failure (POF) in mice. However, its role in POF patients is unclear. We predicted that miR-146b-5p might interact with lncRNA DLEU1, a crucial player in ovarian cancer. We then explored the interaction between DLEU1 and miR-146b-5p.

Methods: Expression of DLEU1 and miR-146b-5p in POF and control ovary tissues was determined by RT-qPCR. The subcellular location of DLEU1 in human KGN cells was analyzed using subcellular fractionation assays. The direct interaction between DLEU1 and miR-146b-5p was analyzed using RNA pull-down assays. The role of DLEU1 in miR-146a expression was analyzed using overexpression assay. Cell proliferation was analyzed using cell apoptosis assay.

Results: Increased DLEU1 expression and decreased miR-146b-5p expression were observed in POF. DLEU1 directly interacted with MiR-146b-5p and was expressed in both nuclear and cytoplasm samples of KGN cells. In KGN cells, DLEU1 and miR-146b-5p failed to regulate the expression of each other. However, DLEU1 promoted cell apoptosis and reduced the inhibitory effects of miR-146b-5p on cell apoptosis.

Conclusions: DLEU1 is overexpressed in POF and sponges miR-146b-5p to increase KGN cell apoptosis.

Keywords: DLEU1; POF; Premature ovarian failure; miR-146b-5p.

MeSH terms

  • Adult
  • Anti-Mullerian Hormone / blood
  • Apoptosis / genetics*
  • Case-Control Studies
  • Cell Proliferation / genetics*
  • Estradiol / blood
  • Female
  • Follicle Stimulating Hormone / blood
  • Granulosa Cells*
  • Humans
  • Luteinizing Hormone / blood
  • MicroRNAs / genetics*
  • Primary Ovarian Insufficiency / blood
  • Primary Ovarian Insufficiency / genetics*
  • RNA, Long Noncoding / genetics*

Substances

  • DLEU1 lncRNA, human
  • MIRN146 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Estradiol
  • Anti-Mullerian Hormone
  • Luteinizing Hormone
  • Follicle Stimulating Hormone