dbEMT 2.0: An updated database for epithelial-mesenchymal transition genes with experimentally verified information and precalculated regulation information for cancer metastasis

Zhao, Min; Liu, Yining; Zheng, Chong; Qu, Hong

doi:10.1016/j.jgg.2019.11.010

Cited by 72 publications

(74 citation statements)

References 8 publications

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“…Given these observations, we were intrigued by our finding that TGFB2 was up-regulated in the t-rRPE and rRPE, leading us to speculate a possible role for EMT in initiating embryonic RPE reprogramming (Supplementary Files S1,2). To test this hypothesis, we performed gene set enrichment analysis (GSEA) using dbEMT 2.0, a curated compendium of EMT-associated genes, from which we identified 839 chicken orthologs [40, 42]. Surprisingly, GSEA revealed a significant enrichment of the EMT-associated genes expressed in the regenerative rRPE relative to the non-regenerative t-rRPE (Figure 5a).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome profiling of embryonic retinal pigment epithelium reprogramming

Tangeman

Luz-Madrigal

Sreeskandarajan

et al. 2021

Preprint

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The plasticity of human retinal pigment epithelium (RPE) has been observed during proliferative vitreoretinopathy, a defective repair process during which injured RPE gives rise to fibrosis. In contrast, following injury, the RPE of the embryonic chicken can be reprogrammed to regenerate neural retina in an FGF2-dependent manner. To characterize the mechanisms underlying embryonic RPE reprogramming, we used laser capture microdissection to isolate RNA from 1) intact RPE, 2) transiently reprogrammed RPE (t-rRPE) 6 hours post-retinectomy, and 3) reprogrammed RPE (rRPE) 6 hours post-retinectomy with FGF2 treatment. Using RNA-seq, we observed the acute repression of genes related to cell cycle progression in the injured t-rRPE, as well as up-regulation of genes associated with injury. In contrast, the rRPE was strongly enriched for MAPK-responsive genes and retina development factors, confirming that FGF2 and the downstream MAPK cascade are the main drivers of embryonic RPE reprogramming. Clustering and pathway enrichment analysis were used to create an integrated network of the core processes associated with RPE reprogramming, including key terms pertaining to injury response, migration, actin dynamics, and cell cycle progression. Finally, we employed gene set enrichment analysis to suggest a previously uncovered role for epithelial-mesenchymal transition (EMT) machinery in the initiation of embryonic chick RPE reprogramming. The EMT program is accompanied by extensive, coordinated regulation of extracellular matrix (ECM) regulators, and these observations together suggest an early role for ECM and EMT-like dynamics during reprogramming. Our study provides for the first time an in-depth transcriptomic analysis of embryonic RPE reprogramming and will prove useful in guiding future efforts to understand proliferative disorders of the RPE and to promote retinal regeneration.

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Section: Resultsmentioning

confidence: 99%

Transcriptome profiling of embryonic retinal pigment epithelium reprogramming

Tangeman

Luz-Madrigal

Sreeskandarajan

et al. 2021

Preprint

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“…To answer this, the following fundamental question must first be answered: what is the EMT/MET molecular profiles in terms of cell fate conversion from fibroblasts to hPSCs? The recent tallying indicates that as many as 1184 genes are involved in the EMT/MET processes [ 39 ]. EMT and its reverse process MET occur during different stages of development for organogenesis (type I), wound healing and fibrosis (type II), and cancer progression (type III) [ 40 ].…”

Section: Resultsmentioning

confidence: 99%

“…The complete list of 1184 human genes related to MET/EMT was downloaded from the EMT database, dbEMT2.0 [ 39 ]. This gene set was used to define the EMT/MET gene expression profiles in hPSCs and fibroblasts, and then the MET subreprogramomes for reprogramming of human fibroblasts into HiPSCs using the RNA-seq data of hESCs and fibroblasts.…”

Section: Methodsmentioning

confidence: 99%

Quick, Coordinated and Authentic Reprogramming of Ribosome Biogenesis during iPSC Reprogramming

2020

Cells

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Induction of pluripotent stem cells (iPSC) by OCT4 (octamer-binding transcription factor 4), SOX2 (SR box 2), KLF4 (Krüppel-Like Factor 4), and MYC (cellular Myelocytomatosis, c-MYC or MYC) (collectively OSKM) is revolutionary, but very inefficient, slow, and stochastic. It is unknown as to what underlies the potency aspect of the multi-step, multi-pathway, and inefficient iPSC reprogramming. Mesenchymal-to-epithelial (MET) transition is known as the earliest pathway reprogrammed. Using the recently established concepts of reprogramome and reprogramming legitimacy, the author first demonstrated that ribosome biogenesis (RB) is globally enriched in terms of human embryonic stem cells in comparison with fibroblasts, the popular starting cells of pluripotency reprogramming. It is then shown that the RB network was reprogrammed quickly in a coordinated fashion. Human iPSCs also demonstrated a more robust ribosome biogenesis. The quick and global reprogramming of ribosome biogenesis was also observed in an independent fibroblast line from a different donor. This study additionally demonstrated that MET did not initiate substantially at the time of proper RB reprogramming. This quick, coordinated and authentic RB reprogramming to the more robust pluripotent state by the OSKM reprogramming factors dramatically contrasts the overall low efficiency and long latency of iPSC reprogramming, and aligns well with the potency aspect of the inefficient OSKM reprogramming.

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“…We also asked if there is a risk of highly aggressive and drug-resistant tumors associated with CR-responded DEGs in DM epithelial cells. Figure 2B shows that using the dbEMT, an epithelial-mesenchymal transition (EMT) associated gene resource (35), CR DEGs were classified as: oncogenic EMT-related genes (CR upregulated: Aldh1a1, Aldh1a7, Srebf1; CR downregulated: Ros1, Muc4) and tumor-suppressive EMT-related genes (CR downregulated: Ceacam2, Mir200b, Arhgef12, Stat1, Baft2, Sirt3, Sod2; CR upregulated: Angptl4, Ndrg1, Fbp1, Tgfbr2, Pebp1). Skil (suppressed upon CR), was classified as an EMT-related gene with dual roles (oncogenic and tumor-suppressive function).…”

Section: % Of Cr Response Genes Are Involved In Mucosa Normal-adenomentioning

confidence: 99%

Immunity Depletion, Telomere Imbalance, and Cancer-associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Caloric Restriction

Maestri

Duszka

Kuznetsov

2021

Preprint

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Systematic analysis of calorie restriction (CR) mechanisms and pathways in cancer biology has not been carried out, leaving therapeutic benefits unclear. Using a systems biology approach and metadata analysis, we studied gene expression changes in the response of normal mouse duodenum mucosa (DM) to short-term (2-weeks) 25% CR as a biological model. We found a high similarity of gene expression profiles in human and mouse DM tissues. Surprisingly, 26% of the 467 CR responding differential expressed genes (DEGs) in mice consist of cancer-associated genes, most never studied in CR contexts. The DEGs were enriched with over-expressed cell cycle, oncogenes, and metabolic reprogramming pathways (MRP) that determine tissue-specific tumorigenesis, cancer, and stem cell activation; tumor suppressors and apoptosis genes were under-expressed. DEG enrichments suggest a misbalance in telomere maintenance and activation of metabolic pathways playing dual (anti-cancer and pro-oncogenic) roles. Immune system genes (ISGs) consist of 37% of the total DEGs; the majority of ISGs are suppressed, including cell-autonomous immunity and tumor immune evasion controls. Thus, CR induces MRP suppressing multiple immune mechanics and activating oncogenic pathways, potentially driving pre-malignant and cancer states. These findings may change the paradigm regarding the anti-cancer role of CR and initiate specific treatment target development.

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dbEMT 2.0: An updated database for epithelial-mesenchymal transition genes with experimentally verified information and precalculated regulation information for cancer metastasis

Cited by 72 publications

References 8 publications

Transcriptome profiling of embryonic retinal pigment epithelium reprogramming

Transcriptome profiling of embryonic retinal pigment epithelium reprogramming

Quick, Coordinated and Authentic Reprogramming of Ribosome Biogenesis during iPSC Reprogramming

Immunity Depletion, Telomere Imbalance, and Cancer-associated Metabolism Pathway Aberrations in Intestinal Mucosa upon Caloric Restriction

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