title: Integrative transcriptome analysis reveals dysregulation of canonical cancer molecular pathways in placenta leading to preeclampsia.
abstract: We previously suggested links between specific XPD mutations in the fetal genome and the risk of placental maldevelopment and preeclampsia, possibly due to impairment of Transcription Factor (TF)IIH-mediated functions in placenta. To identify the underlying mechanisms, we conducted the current integrative analysis of several relevant transcriptome data sources. Our meta-analysis revealed downregulation of TFIIH subunits in preeclamptic placentas. Our overall integrative analysis suggested that, in the presence of hypoxia and oxidative stress, EGFR signaling deficiency, which can be caused by TFIIH impairment as well as by other mechanisms, results in ATF3 upregulation, inducing mediators of clinical symptoms of preeclampsia such as FLT1 and ENG. EGFR- and ATF3-dependent pathways play prominent roles in cancer development. We propose that dysregulation of these canonical cancer molecular pathways occurs in preeclampsia and delineate the relevance of TFIIH, providing etiologic clues which could eventually translate into a therapeutic approach.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, NY 12144, USA. rmoslehi@albany.edu
authors.forename: Roxana
authors.initials: R
authors.lastname: Moslehi
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.forename: Caroline
authors.initials: C
authors.lastname: Signore
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
authors.forename: Xavier
authors.initials: X
authors.lastname: Ambroggio
authors.forename: Amiran
authors.initials: A
authors.lastname: Dzutsev
mesh_terms: D000328:Adult; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism*; D011247:Pregnancy; D014157:Transcription Factors / Q000378:metabolism*; D059467:Transcriptome; D055815:Young Adult
chemical_list: D009363:Neoplasm Proteins; D014157:Transcription Factors