FOXN3 Enlists NEAT1-containing SIN3A Complex to Regulate Mammary Epithelium Differentiation and Promote Breast Cancer Metastasis
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PROVIDER: PRJNA362347 | ENA |
REPOSITORIES: ENA
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Project description:The forkhead box (FOX) family of proteins is composed of more than 50 members that are phylogenetically classified into 19 subclasses (A to S). These transcription factors all share a homology in their DNA-binding domain, the forkhead domain, also known as winged helix due to its butterfly-like structural appearance.FOX proteins have been implicated in a broad spectrum of cellular processes including cell proliferation, differentiation, DNA repair, metabolism, and aging. However, the biological function of the mammalian forkhead transcription factors of the N class including FOXN3 remains to be investigated. The SIN3A complex is a large protein assembly consisting of over a dozen of proteins including SIN3A, HDAC1/2, RBBP4/7 and etc. This complex is recruited by multiple transcription repressors and impacts on multifaceted biological functions ranging from development, differentiation, and senescence to oncogenic transformation. Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that are over 200 nucleotides in length. In the past years, these molecules have emerged as important components of the epigenetic regulatory network to influence transcription as well as other nuclear activities, and their dysregulation underlies several pathologic states including cancer. One of the lncRNAs, NEAT1 (nuclear paraspeckle assembly transcript 1), is a highly abundant lncRNA initially described as a structural component of nuclear paraspeckles. Subsequent studies suggest that NEAT1 also influences transcription through either an indirect mechanism or a direct way. In this study, we investigated the function and the underlying mechanism of FOXN3 in breast cancer cells. We showed that FOXN3 is physically associated with the SIN3A complex and identified that NEAT1, which is induced by estrogen in breast cancer cells, is required for this interaction. We analyzed the genomic targets of the FOXN3/SIN3A/NEAT1 complex and demonstrated that estrogen receptor (ER) itself is regulated, through negative feedback, by the FOXN3/SIN3A/NEAT1 complex. We investigated the role of the FOXN3/SIN3A/NEAT1 complex in breast cancer metastasis and explored the clinicopathological significance of the ER-NEAT1-FOXN3/NEAT1/SIN3A-GATA3 axis in breast cancer.
2017-06-01 | GSE93780 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-06-01 | GSE93781 | GEO
Project description: Not available
| S-EPMC5669564 | biostudies-literature
Project description:We sequenced mRNA from livers of 7 dpf transgenic zebrafish overexpressing foxn3 (in the liver) and non-transgenic siblings
2016-04-10 | GSE80003 | GEO
Project description:Sin3a is the central scaffold protein of the prototypical Hdac1/2 chromatin repressor complex, crucially required during early embryonic development for the growth of pluripotent cells of the inner cell mass. Here, we explore the endogenous composition of the Sin3a-Hdac complex in pluripotent embryonic stem (ES) and differentiated cells. To do this, we established an endogenous double immunoprecipitation strategy coupled with quantitative mass spectrometry (ENDIP-MS) allowing us to define the precise composition of the Sin3a complex in multiple cell types. We identify the Fam60a subunit as a key defining feature of a variant Sin3a complex present in ES cells, but not in differentiated cells. Fam60a co-occupies H3K4me3 positive promoters with Sin3a and is essential to maintain it on chromatin. Consistent with this, Fam60a depletion phenocopies the loss of Sin3a, leading to decreased proliferation, an extended G1-phase and the deregulation of genes associated with differentiation. Taken together, our data characterise Fam60a as an essential core subunit of a variant Sin3a complex in ES cells required to promote rapid proliferation and to prevent unscheduled differentiation.
2017-05-19 | PXD005464 | Pride
Project description:The mammalian retina contains a complex mixture of different types of neurons. We find that the microRNA miR-216b is preferentially expressed in postmitotic retinal amacrine cells in the mouse retina, and expression of miR-216a/b and miR-217 in the retina depend in part on Ptf1a, a transcription factor required for amacrine cell differentiation. Surprisingly, ectopic expression of miR-216b, or the related miR-216a, can direct the formation of additional amacrine cells in the developing retina. In addition, we observe the loss of bipolar neurons in the retina after miR-216b expression. We identify the mRNA for the transcriptional regulator Foxn3 as a retinal target of miR-216b by Argonaute PAR-CLIP and reporter analysis. Inhibition of Foxn3 in the postnatal developing retina by RNAi also increases the formation of amacrine cells and reduces bipolar cell formation, while overexpression of Foxn3 inhibits amacrine cell formation prior to the expression of Ptf1a. Disruption of Foxn3 by CRISPR in embryonic retinal explants also reduces amacrine cell formation. Co-expression of Foxn3 partially reverses the effects of ectopic miR-216b on retinal cell type formation. Our results identify Foxn3 as a novel regulator of interneuron formation in the developing retina and suggest that miR-216b likely regulates expression of Foxn3 and other genes in amacrine cells.
2021-12-22 | GSE165827 | GEO
Project description:The mammalian retina contains a complex mixture of different types of neurons. We find that the microRNA miR-216b is preferentially expressed in postmitotic retinal amacrine cells in the mouse retina, and expression of miR-216a/b and miR-217 in the retina depend in part on Ptf1a, a transcription factor required for amacrine cell differentiation. Surprisingly, ectopic expression of miR-216b, or the related miR-216a, can direct the formation of additional amacrine cells in the developing retina. In addition, we observe the loss of bipolar neurons in the retina after miR-216b expression. We identify the mRNA for the transcriptional regulator Foxn3 as a retinal target of miR-216b by Argonaute PAR-CLIP and reporter analysis. Inhibition of Foxn3 in the postnatal developing retina by RNAi also increases the formation of amacrine cells and reduces bipolar cell formation, while overexpression of Foxn3 inhibits amacrine cell formation prior to the expression of Ptf1a. Disruption of Foxn3 by CRISPR in embryonic retinal explants also reduces amacrine cell formation. Co-expression of Foxn3 partially reverses the effects of ectopic miR-216b on retinal cell type formation. Our results identify Foxn3 as a novel regulator of interneuron formation in the developing retina and suggest that miR-216b likely regulates expression of Foxn3 and other genes in amacrine cells.
2021-12-22 | GSE165831 | GEO
Project description:The mammalian retina contains a complex mixture of different types of neurons. We find that the microRNA miR-216b is preferentially expressed in postmitotic retinal amacrine cells in the mouse retina, and expression of miR-216a/b and miR-217 in the retina depend in part on Ptf1a, a transcription factor required for amacrine cell differentiation. Surprisingly, ectopic expression of miR-216b, or the related miR-216a, can direct the formation of additional amacrine cells in the developing retina. In addition, we observe the loss of bipolar neurons in the retina after miR-216b expression. We identify the mRNA for the transcriptional regulator Foxn3 as a retinal target of miR-216b by Argonaute PAR-CLIP and reporter analysis. Inhibition of Foxn3 in the postnatal developing retina by RNAi also increases the formation of amacrine cells and reduces bipolar cell formation, while overexpression of Foxn3 inhibits amacrine cell formation prior to the expression of Ptf1a. Disruption of Foxn3 by CRISPR in embryonic retinal explants also reduces amacrine cell formation. Co-expression of Foxn3 partially reverses the effects of ectopic miR-216b on retinal cell type formation. Our results identify Foxn3 as a novel regulator of interneuron formation in the developing retina and suggest that miR-216b likely regulates expression of Foxn3 and other genes in amacrine cells.
2021-12-22 | GSE165830 | GEO
Project description:Radioresistance is one of the main factors that lead to the failure of radiotherapy in lung cancer patients. The mechanisms underlying these processes are, however, not fully understood. Here, we find that the low levels of FOXN3 protein is associated with poor prognosis of lung cancer patients. Furthermore, we show that depletion of FOXN3 promotes DNA damage repair and confers lung cancer radioresistance in a BRCA1-dependent manner. Mechanistically, we uncover that E3 ligase β-Trcp and protein kinase RSK2 bind to and cooperatively induce the ubiquitin-mediated degradation of FOXN3. More importantly, β-Trcp and RSK2-mediated ubiquitination of FOXN3 facilitate DNA damage repair in lung cancer. Thus, our findings reveal the molecular mechanism to control the abundance of FOXN3 in DNA damage repair, indicating that targeting β-Trcp/RSK2/FOXN3/BRCA-1 axis may be a novel radiosensitization strategy in lung cancer.
2023-06-30 | GSE218171 | GEO
Project description:Although thousands of long non-coding RNAs (lncRNAs) are localized in the nucleus, only a few dozen have been functionally characterized. We found that nuclear paraspeckle assembly transcript 1 (NEAT1), an essential lncRNA for the formation of nuclear body paraspeckles, is induced by poly I:C stimulation, resulting in excess formation of paraspeckles. Using microarray analysis, we investigated whether NEAT1 induction followed by excess formation of paraspeckles was involved in poly I:C-inducible gene expression. We want to know the NEAT1-regulated genes. To the end, HeLa TO cells with and without poly I:C stimulation and NEAT1-knock down cells with and without poly I:C stimulation and cells transfected with mock plasmid or Neat1v2 expression plasmid alone were used for RNA extraction and hybridization on Affymetrix microarrays.
2014-05-07 | E-GEOD-56936 | biostudies-arrayexpress