MicroRNA‑155‑5p inhibits trophoblast cell proliferation and invasion by disrupting centrosomal function

Mol Med Rep. 2024 May;29(5):85. doi: 10.3892/mmr.2024.13209. Epub 2024 Mar 29.

Abstract

Recurrent miscarriage is used to refer to more than three pregnancy failures before 20 weeks of gestation. Defective trophoblast cell growth and invasion are frequently observed in recurrent miscarriage. Several microRNAs (miRs), including miR‑155‑5p, are aberrantly upregulated in recurrent miscarriage; however, the underlying molecular mechanisms remain unclear. The centrosome orchestrates microtubule networks and coordinates cell cycle progression. In addition, it is a base for primary cilia, which are antenna‑like organelles that coordinate signaling during development and growth. Thus, deficiencies in centrosomal functions can lead to several disease, such as breast cancer and microcephaly. In the present study, the signaling cascades were analyzed by western blotting, and the centrosome and primary cilia were observed and analyzed by immunofluorescence staining. The results showed that overexpression of miR‑155‑5p induced centrosome amplification and blocked primary cilia formation in trophoblast cells. Notably, centrosome amplification inhibited trophoblast cell growth by upregulating apoptotic cleaved‑caspase 3 and cleaved‑poly (ADP‑ribose) polymerase in miR‑155‑5p‑overexpressing trophoblast cells. In addition, overexpression of miR‑155‑5p inhibited primary cilia formation, thereby inhibiting epithelial‑mesenchymal transition and trophoblast cell invasion. All phenotypes could be rescued when cells were co‑transfected with the miR‑155‑5p inhibitor, thus supporting the role of miR‑155‑5p in centrosomal functions. It was also found that miR‑155‑5p activated autophagy, whereas disruption of autophagy via the depletion of autophagy‑related 16‑like 1 alleviated miR‑155‑5p‑induced apoptosis and restored trophoblast cell invasion. In conclusion, the present study indicated a novel role of miR‑55‑5p in mediating centrosomal function in recurrent miscarriage.

Keywords: cell growth; centrosome; invasion; microRNA‑155‑5p; primary cilia; trophoblast.

MeSH terms

  • Abortion, Habitual* / metabolism
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Centrosome / metabolism
  • Female
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pregnancy
  • Trophoblasts / metabolism

Substances

  • MicroRNAs
  • MIRN155 microRNA, human

Grants and funding

The present study was supported by the Ministry of Science and Technology of Taiwan (MOST109-2320-B-006-042-MY3 and NSTC112-2320-B-006-040) and the Chi Mei Medical Center (CMNCKU11108).