Abstract
BackgroundNuclear receptor family member, Estrogen related receptor β, and the Hedgehog signal transduction pathway are both reported to relate to tumorigenesis and induced pluripotent stem cell reprogramming. We hypothesize that Estrogen related receptor β can modulate the Hedgehog signaling pathway and affect Hedgehog driven downstream gene expression.ResultsWe established an estrogen related receptor β-expressing Hedgehog-responsive NIH3T3 cell line by Esrrb transfection, and performed mRNA profiling using RNA-Seq after Hedgehog ligand conditioned medium treatment. Esrrb expression altered 171 genes, while Hedgehog signaling activation alone altered 339 genes. Additionally, estrogen related receptor β expression in combination with Hedgehog signaling activation affects a group of 109 Hedgehog responsive mRNAs, including Hsd11b1, Ogn, Smoc2, Igf1, Pdcd4, Igfbp4, Stmn1, Hp, Hoxd8, Top2a, Tubb4b, Sfrp2, Saa3, Prl2c3 and Dpt.ConclusionsWe conclude that Estrogen related receptor β is capable of interacting with Hh-signaling downstream targets. Our results suggest a new level of regulation of Hedgehog signaling by Estrogen related receptor β, and indicate modulation of Estrogen related receptor β can be a new strategy to regulate various functions driven by the Hedgehog signaling pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12867-015-0047-3) contains supplementary material, which is available to authorized users.
Highlights
Nuclear receptor family member, Estrogen related receptor β, and the Hedgehog signal transduction pathway are both reported to relate to tumorigenesis and induced pluripotent stem cell reprogramming
By employing mRNA profiling, we emphasized on the discovery of Estrogen related receptor β (Esrrb)-regulated Hh-signaling pathwaytargeted genes and we report 109 genes that differentially respond to Hh-signaling activation with Esrrb present
Among tested mRNAs, we found that when Esrrb expressing cells are treated with Hh ligand conditioned medium (Hh-CM), Sfrp2, Saa3, Prl2c3, Stmn1, Hp, Hoxd8, Tubb4b, Top2a and Dpt had different mRNA concentrations compared to Hh-CM treatment in cells without Esrrb
Summary
Estrogen related receptor β, and the Hedgehog signal transduction pathway are both reported to relate to tumorigenesis and induced pluripotent stem cell reprogramming. Hedgehog (Hh) signaling is a pivotal signaling pathway in embryonic pattern formation, stem cell/cancer stem cell self-renewal, as well as induced pluripotent stem cells induction [1,2,3,4,5,6,7,8,9,10,11,12]. An early study showed the Hh-signaling inhibitor, cyclopamine, is enriched in Veratrum californicum. This plant when consumed by pregnant sheep resulted in a midline differentiation defect in offspring [13,14,15,16,17]. The FDA in 2012 approved GDC-0449, an Hh pathway inhibitor targeting Smoothened for basal cell carcinoma treatment [33, 37, 38]
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