MiR-187 regulates the proliferation, migration and invasion of human trophoblast cells by repressing BCL6-mediated activation of PI3K/AKT signaling

Placenta. 2022 Feb:118:20-31. doi: 10.1016/j.placenta.2022.01.001. Epub 2022 Jan 5.

Abstract

Introduction: Recurrent miscarriage (RM), refers to two or more consecutive spontaneous miscarriage in a pregnant woman. RM is caused by many factors, and microRNAs play an important role in the development and pathology of RM. In the present study, we investigated the function of miR-187 in the pathogenesis of RM and its effects on human trophoblast cells.

Methods: The localization of miR-187 in the human placenta in early pregnancy was determined by in situ hybridization. QRT-PCR was used to detect the expression of miR-187 in villi of normal early pregnancy induced abortion group and recurrent spontaneous miscarriage group. Then, HTR8/SVneo cells were used to investigated the effect of miR-187 on BCL6 expression and biological activity of trophoblasts.

Results: We found that the expression of miR-187 in villi of RM group was higher than that of normal abortion group and miR-187 inhibited the proliferation, migration, and invasion of HTR8 cells. We also found that miR-187 promoted apoptosis, inhibited EMT, and inhibited the PI3K/AKT pathway in HTR8 cells. In addition, we also found that BCL6 is a direct target of miR-187 and is negatively regulated by miR-187. In addition, BCL6 reversed the inhibitory effects of miR-187 on HTR8/SVneo cells. These data demonstrate that miR-187-induced repression of PI3K/AKT signaling is mediated by BCL6 in HTR8 cells.

Disscussion: MiR-187 inhibits the proliferation, migration, and invasion of trophoblasts through a mechanism that involves regulation of BCL6.

Keywords: Apoptosis; Migration; Proliferation; Recurrent miscarriage; Trophoblast; miR-187.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / etiology
  • Abortion, Habitual / metabolism*
  • Adult
  • Case-Control Studies
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • MicroRNAs / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pregnancy
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • Trophoblasts / physiology*

Substances

  • BCL6 protein, human
  • MIRN187 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-6
  • Proto-Oncogene Proteins c-akt