Long non-coding RNA SNHG29 regulates cell senescence via p53/p21 signaling in spontaneous preterm birth

Placenta. 2021 Jan 1:103:64-71. doi: 10.1016/j.placenta.2020.10.009. Epub 2020 Oct 15.

Abstract

Introduction: Spontaneous preterm birth affects>5-18% of pregnancies and causes infant morbidity and mortality. Long non-coding RNAs can regulate gene expression and have been associated with preterm birth. In this study, we investigated whether the long non-coding RNA SNHG29 was associated with spontaneous preterm birth.

Methods: We collected the placentas from women who underwent preterm/full-term birth with/without labor. We determined the levels of expression of SNHG29 in the placental tissues using quantitative real-time polymerase chain reaction. We generated a senescence model by treating HTR8/SVneo cells with 200 μM H2O2 for 2 h. The degree of senescence induced in cells depleted of or overexpressing SNHG29 was determined by measuring senescence-associated gene expression and β-galactosidase activity.

Results: SNHG29 was overexpressed in the placentas of women who delivered preterm with labor and in HTR8/SVneo cells treated with H2O2 (p < 0.05). The levels of mRNA of p53 and p21, protein levels of p53, phospho-p53, p21and phospho-p21, and β-galactosidase activity was decreased in HTR8/SVneo cells depleted of SNHG29, while the opposite trend was observed in HTR8/SVneo cells overexpressing SNHG29 (p < 0.05). We observed an increase in the expression of IL-8 and TNF-α in senescent HTR8/SVneo cells (p < 0.05).

Discussion: SNHG29 was overexpressed in placentas from women who delivered preterm with labor compared to those in women who underwent preterm birth without labor and full-term birth with/without labor. High levels of SNHG29 enhanced senescence in vivo. The increase in pro-inflammatory cytokine expression and release by senescent cells may be pivotal to the pathophysiology of spontaneous preterm birth.

Keywords: Cellular senescence; Oxidative stress; SASP; SNHG29; Spontaneous preterm birth; p53/p21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Case-Control Studies
  • Cell Line
  • Cellular Senescence / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Female
  • Humans
  • Infant, Newborn
  • Pregnancy
  • Premature Birth / genetics*
  • Premature Birth / metabolism
  • Premature Birth / pathology
  • RNA, Long Noncoding / physiology*
  • Signal Transduction / genetics
  • Signal Transduction / physiology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Long Noncoding
  • Tumor Suppressor Protein p53