STAT3 cooperates with the non-canonical NF-κB signaling to regulate pro-labor genes in the human placenta

L. J. Yu, B. Wang, N. Parobchak, N. Roche, T. Rosen

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Abstract Introduction Our recent studies have shown that constitutively activated non-canonical RelB/NF-κB2 (p52) in the human placenta positively regulates the pro-labor genes CRH and COX-2. STAT3 regulates NF-κB2 (p100) processing to active p52, and in turn, nuclear activation of RelB/p52, by directly binding to p100/p52 in a variety of cancer cells. In the current study, we tested the hypothesis that STAT3 is involved in regulation of pro-labor genes by associating with RelB/p52 heterodimers in the human placenta. Methods We used a variety of techniques including immunohistochemical staining, gene silencing, ectopic expression, chromatin immunoprecipitation, Western blot, RT-qPCR, and immunofluorescence assays in primary culture of cytotrophoblast and placental tissues. Results We found that knockdown of STAT3 led to down-regulation of both CRH and COX-2 in a dose-dependent manner. By using chromatin immunoprecipitation, we further showed that interaction of RelB with the CRH or COX-2 gene promoters decreased when STAT3 was depleted. Immunofluorescence demonstrated co-localization of STAT3 with RelB or p100/p52 in both the cytoplasm and nucleus of term cytotrophoblasts. Discussion Collectively, these results suggest that STAT3 constitutes part of the RelB/p52-containing activator complex that positively regulates pro-labor genes in the human placenta.

Original languageEnglish (US)
Article number3168
Pages (from-to)581-586
Number of pages6
JournalPlacenta
Volume36
Issue number5
DOIs
StatePublished - May 1 2015

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Developmental Biology

Keywords

  • Non-canonical NF-kB
  • Pro-labor genes
  • STAT3

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