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LncRNA SCIRT acts in a negative feedback loop to regulate the transcriptional program for cancer self-renewal

ABSTRACT: LncRNA SCIRT acts in a negative feedback loop to regulate the transcriptional program for cancer self-renewal

PROVIDER: PRJNA561574 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10044637.fastq.gz	Fastqsanger.gz
	SRR10044638.fastq.gz	Fastqsanger.gz
	SRR10044639.fastq.gz	Fastqsanger.gz
	SRR10044640.fastq.gz	Fastqsanger.gz
	SRR10044641.fastq.gz	Fastqsanger.gz

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The MAPK14/MAPK7/BCL6B pathway creates a positive feedback loop to drive spermatogonial stem cell (SSC) self-renewal via ROS amplification.

Project description:Reactive oxygen species (ROS) play critical roles in self-renewal division for various stem cell types. However, it remains unclear how ROS signals are integrated with self-renewal machinery. Here we report that the MAPK14/MAPK7/BCL6B pathway creates a positive feedback loop to drive spermatogonial stem cell (SSC) self-renewal via ROS amplification. The activation of MAPK14 induced MAPK7 phosphorylation in cultured SSCs, and targeted deletion of Mapk14 or Mapk7 resulted in significant SSC deficiency after spermatogonial transplantation. The activation of this signaling pathway not only induced Nox1 but also increased ROS levels. Chemical screening of MAPK7 targets revealed many ROS-dependent spermatogonial transcription factors, of which BCL6B was found to initiate ROS production by increasing Nox1 expression via ETV5-induced nuclear translocation. Because hydrogen peroxide or Nox1 transfection also induced BCL6B nuclear translocation, our results suggest that BCL6B initiates and amplifies ROS signals to activate ROS-dependent spermatogonial transcription factors by forming a positive feedback loop.

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LncRNA SCIRT acts in a negative feedback loop to regulate the transcriptional program for cancer self-renewal

Project description:This SuperSeries is composed of the SubSeries listed below.

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ROS amplification drives mouse spermatogonial stem cell self-renewal

Project description:Reactive oxygen species (ROS) play critical roles in self-renewal division for various stem cell types. However, it remains unclear how ROS signals are integrated with selfrenewal machinery. Here we report that the MAPK14/MAPK7/BCL6B pathway creates a positive feedback loop to drive spermatogonial stem cell (SSC) self-renewal via ROS amplification. The activation of MAPK14 induced MAPK7 phosphorylation in cultured SSCs, and targeted deletion of Mapk14 or Mapk7 resulted in significant SSC deficiency after spermatogonial transplantation. The activation of this signaling pathway not only induced Nox1 but also increased ROS levels. Chemical screening of MAPK7 targets revealed many ROS-dependent spermatogonial transcription factors, of which BCL6B was found to initiate ROS production by increasing Nox1 expression via ETV5-induced nuclear translocation. Because hydrogen peroxide or Nox1 transfection also induced BCL6B nuclear translocation, our results suggest that BCL6B initiates and amplifies ROS signals to activate ROS-dependent spermatogonial transcription factors by forming a positive feedback loop.

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Project description:PRH/HHEX-Notch3 feedback loop drives cholangiocarcinoma

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The MAPK14/MAPK7/BCL6B pathway creates a positive feedback loop to drive spermatogonial stem cell (SSC) self-renewal via ROS amplification.

Project description:The MAPK14/MAPK7/BCL6B pathway creates a positive feedback loop to drive spermatogonial stem cell (SSC) self-renewal via ROS amplification.

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Alternative Splicing of MBD2 Supports Self-Renewal in Human Pluripotent Stem Cells [HJAY]

Project description:Alternative RNA splicing (AS) regulates proteome diversity, including isoform-specific expression of several pluripotency genes. Here, we integrated global gene expression and proteomic analyses and identified a molecular signature suggesting a central role for AS in maintaining human pluripotent stem cell (hPSC) self-renewal. We demonstrate the splicing factor SFRS2 is an OCT4 target gene required for pluripotency. SFRS2 regulates AS of the methyl-CpG-binding protein MBD2, whose isoforms play opposing roles in maintenance of, and reprogramming to, pluripotency. While both MDB2a and MBD2c are enriched at the OCT4 and NANOG promoters, MBD2a preferentially interacts with repressive NuRD chromatin remodeling factors and promotes hPSC differentiation, whereas overexpression of MBD2c enhances reprogramming of fibroblasts to pluripotency. The miR-301 and miR-302 families provide additional regulation by targeting SFRS2 and MDB2a. These data suggest that OCT4, SFRS2, and MBD2 participate in a positive feedback loop, regulating proteome diversity complexity in support of hPSC self-renewal and reprogramming. We isolated RNA from human fibroblasts and human embryonic stem cells for hybridization to the Affymetrix gene expression microarrays.

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Analyses of RNAi-heterochromatin positive feedback loop in Tetrahymena

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Alternative Splicing of MBD2 Supports Self-Renewal in Human Pluripotent Stem Cells [HG-U133_Plus_2]

Project description:Using global gene expression and proteomic analyses, we identified a molecular signature in human embryonic and induced pluripotent stem cells that suggested a central regulatory role for RNA splicing in self-renewal. Through genetic and biochemical approaches, we established reciprocal functional links between the master regulatory factor OCT4 and SFRS2, a member of the serine/arginine-rich family of splicing factors. SFRS2 regulates expression of two isoforms of the methyl-CpG-binding protein MBD2 that play opposing roles in human ESC and during the reprogramming of fibroblasts. Both the MBD2a isoform expressed in fibroblasts and the MBD2c isoform found in pluripotent cells bind OCT4 and NANOG promoters in human ESC, but only MBD2a interacts with NuRD chromatin remodeling factors. Members of the miR-301 and miR-302 families provide additional regulation by targeting SFRS2 and the somatic specific MBD2a isoform. These data are consistent with a model in which OCT4, SFRS2, and MBD2 participate in a positive feedback loop to regulate proteome diversity in support of self-renewal in pluripotent cells. We isolated RNA from human iPS cells, different human fibroblasts and human embryonic stem cells for hybridization to the Affymetrix gene expression microarrays.

2014-04-18 | E-GEOD-55673 | biostudies-arrayexpress

Epigenetic regulation of iASPP-p63 feedback loop in cutaneous squamous cell carcinoma

Project description:Keratinocyte skin cancer, comprising cutaneous squamous (cSCC) and basal cell carcinoma, is the most common malignancy in the UK. P53 is frequently mutated in cSCC. iASPP is a key inhibitor of p53 and NF-kB signalling pathways and has been documented as highly expressed in several types of human cancer. We have previously identified an autoregulatory feedback loop between iASPP and p63, which is critical in epidermal homeostasis. We hypothesised a potential role for dysregulation of this axis in the pathogenesis of keratinocyte malignancies. Immunostaining of 116 cSCC clinical samples revealed increased iASPP and ΔNp63 expression but also highlighted a significant alteration of iASPP cellular localisation, with consequent deregulation of its function. Expression patterns, functionality, gene and microRNA expression analysis were further investigated in 10 cSCC cell lines. Our data suggest that whilst direct effects of iASPP and p63 upon each other’s expression are maintained in cSCC, epigenetic dysregulation of the feedback loop occurs at the microRNA level by a novel mechanism controlling p63 expression. We demonstrate that this autoregulatory feedback loop controls cell migration in cSCC by blocking EMT and promoting proliferation, and provides future directions for clinical biomarker and therapeutic target discovery in cutaneous SCC.

2019-11-20 | GSE123189 | GEO

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