The Long Non-Coding RNA Gene AC027288.3 Plays a Role in Human Endometrial Stromal Fibroblast Decidualization

Cells. 2024 May 2;13(9):778. doi: 10.3390/cells13090778.

Abstract

During the secretory phase of the menstrual cycle, endometrial fibroblast cells begin to change into large epithelial-like cells called decidual cells in a process called decidualization. This differentiation continues more broadly in the endometrium and forms the decidual tissue during early pregnancy. The cells undergoing decidualization as well as the resulting decidual cells, support successful implantation and placentation during early pregnancy. This study was carried out to identify new potentially important long non-coding RNA (lncRNA) genes that may play a role in human endometrial stromal fibroblast cells (hESF) undergoing decidualization in vitro, and several were found. The expression of nine was further characterized. One of these, AC027288.3, showed a dramatic increase in the expression of hESF cells undergoing decidualization. When AC027288.3 expression was targeted, the ability of the cells to undergo decidualization as determined by the expression of decidualization marker protein-coding genes was significantly altered. The most affected markers of decidualization whose expression was significantly reduced were FOXO1, FZD4, and INHBA. Therefore, AC027288.3 may be a major upstream regulator of the WNT-FOXO1 pathway and activin-SMAD3 pathways previously shown as critical for hESF decidualization. Finally, we explored possible regulators of AC027288.3 expression during human ESF decidualization. Expression was regulated by cAMP and progesterone. Our results suggest that AC027288.3 plays a role in hESF decidualization and identifies several other lncRNA genes that may also play a role.

Keywords: decidualization; endometrium; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Differentiation / genetics
  • Decidua* / cytology
  • Decidua* / metabolism
  • Endometrium* / cytology
  • Endometrium* / metabolism
  • Female
  • Fibroblasts* / cytology
  • Fibroblasts* / metabolism
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism
  • Humans
  • Pregnancy
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Stromal Cells* / cytology
  • Stromal Cells* / metabolism

Substances

  • RNA, Long Noncoding
  • Forkhead Box Protein O1
  • FOXO1 protein, human

Grants and funding

This work was supported by the National Institutes of Health (Eunice Kennedy Shriver National Institute of Child Health and Human Development; HD049010 to B.M.B.; HD073868 to D.T.; and HD087973 to L.M.). We would also like to acknowledge additional support from the Southern Illinois University-Carbondale Office of the Vice Chancellor for Research (Research-Enriched Academic Challenge Award to K.M. and B.M.B.) and the Department of Physiology Southern Illinois University School of Medicine (to R.T.).