MiR-93 Inhibits Trophoblast Cell Proliferation and Promotes Cell Apoptosis by Targeting BCL2L2 in Recurrent Spontaneous Abortion

Reprod Sci. 2020 Jan;27(1):152-162. doi: 10.1007/s43032-019-00003-w. Epub 2020 Jan 1.

Abstract

Recurrent spontaneous abortion (RSA) is a common health problem that affects 1-5% of women in reproductive age. Plenty of studies have indicated that microRNAs (miRNAs) are involved in the occurrence of miscarriage. MiR-93 has a wide range of functions in mammalian tissues and plays an important role in many diseases especially for cancers. However, it remains unknown whether miR-93 is associated with human RSA. In this report, clinical samples revealed that miR-93 expression was significantly elevated in the villi tissues of RSA patients. Upregulation of miR-93 inhibited human trophoblast cells HTR-8/SVneo cell proliferation, migration, and invasiveness, but promoted cell apoptosis in vitro. Conversely, the downregulation of miR-93 reversed these effects. Bcl-2 like protein 2 (BCL2L2), a potential target gene of miR-93, was inversely correlated with miR-93 expression in the villi of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-93 directly downregulated the expression of BCL2L2 by binding a specific sequence of its 3'-untranslated region (3'UTR). Collectively, these data strongly suggest that miR-93 regulates trophoblast cell proliferation, migration, invasive, and apoptosis by targeting BCL2L2 expression and is involved in the pathogenesis of RSA.

Keywords: BCL2L2; Recurrent spontaneous abortion; Trophoblast cells; miR-93.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / metabolism*
  • Adult
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Line
  • Cell Proliferation / physiology*
  • Female
  • Humans
  • MicroRNAs / metabolism*
  • Pregnancy
  • Trophoblasts / cytology
  • Trophoblasts / metabolism*
  • Up-Regulation

Substances

  • Apoptosis Regulatory Proteins
  • BCL2L2 protein, human
  • MIRN93 microRNA, human
  • MicroRNAs