title: STAT3 cooperates with the non-canonical NF-κB signaling to regulate pro-labor genes in the human placenta.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal-Fetal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Yu
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal-Fetal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA. Electronic address: wangbi@rwjms.rutgers.edu.
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal-Fetal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA.
authors.forename: N
authors.initials: N
authors.lastname: Parobchak
authors.affiliation: Department of Obstetrics, Gynecology, and Women's Health, Rutgers New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: N
authors.initials: N
authors.lastname: Roche
authors.affiliation: Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal-Fetal Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA. Electronic address: rosentj@rwjms.rutgers.edu.
authors.forename: T
authors.initials: T
authors.lastname: Rosen
mesh_terms: D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D052003:NF-kappa B p52 Subunit / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000378:metabolism; D014590:Uterine Contraction
chemical_list: D052003:NF-kappa B p52 Subunit; C498206:NFKB2 protein, human; C497593:RELB protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051841:Transcription Factor RelB; D003346:Corticotropin-Releasing Hormone; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Non-canonical NF-kB; Pro-labor genes; STAT3