Regulatory Roles for Long ncRNA and mRNA

Karapetyan, Armen R.; Buiting, Coen; Kuiper, Renske A.; Coolen, Marcel W.

doi:10.3390/cancers5020462

Cited by 91 publications

(75 citation statements)

References 185 publications

(265 reference statements)

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“…10-14 However, several other models of context dependent PRC2 recruitment mechanisms, including Polycomb response elements (PREs) 15-18 and ncRNAs [19][20][21][22] have been investigated.…”

Section: Compliance With Ethicsmentioning

confidence: 99%

“…The repression is further maintained through ubiquitination of lysine 119 residue on histone H2A (H2AK119ub) by RING1, a subunit of PRC1, or chromatin condensation. [7][8][9] Promoters of the polycomb target genes have been generally characterised as CpG-rich DNA sequences that are lacking other epigenetic markers.10-14 However, several other models of context dependent PRC2 recruitment mechanisms, including Polycomb response elements (PREs) 15-18 and ncRNAs [19][20][21][22] have been investigated. …”

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confidence: 99%

“…[7][8][9] Promoters of the polycomb target genes have been generally characterised as CpG-rich DNA sequences that are lacking other epigenetic markers. [10][11][12][13][14] However, several other models of context dependent PRC2 recruitment mechanisms, including Polycomb response elements (PREs) [15][16][17][18] and ncRNAs [19][20][21][22] have been investigated.…”

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confidence: 99%

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Bmi1 – A Path to Targeting Cancer Stem Cells

Bakhshinyan¹,

Adile²,

Venugopal³

et al. 2017

European Oncology &Amp; Haematology

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T he Polycomb group (PcG) genes encode for proteins comprising two multiprotein complexes, Polycomb repressive complex 1 (PRC1) and Polycomb repressive complex 2 (PRC2). Although the initial discovery of PcG genes was made in Drosophila, as transcriptional repressors of homeotic (HOX) genes. Polycomb repressive complexes have been since implicated in regulating a wide range of cellular processes, including differentiation and self-renewal in normal and cancer stem cells. Bmi1, a subunit of PRC1, has been long implicated in driving self-renewal, the key property of stem cells. Subsequent studies showing upregulation of Bmi1 in several cancers correlated with increased aggressiveness, radioresistance and metastatic potential, provided rationale for development of targeted therapies against Bmi1. Although Bmi1 activity can be reduced through transcriptional, post-transcriptional and post-translational regulation, to date, the most promising approach has been through small molecule inhibitors targeting Bmi1 activity. The post-translational targeting of Bmi1 in colorectal carcinoma, lung adenocarcinoma, multiple myeloma and medulloblastoma have led to significant reduction of self-renewal capacity of cancer stem cells, leading to slower tumour progression and reduced extent of metastatic spread. Further value of Bmi1 targeting in cancer can be established through trials evaluating the combinatorial effect of Bmi1 inhibition with current 'gold standard' therapies. KeywordsPolycomb group (PcG) genes, Bmi1, Mel-18, cancer stem cells (CSCs), self-renewal Disclosure: David Bakhshinyan, Ashley A Adile, Chitra Venugopal and Sheila K Singh have nothing to disclose in relation to this article.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Compliance with Ethics:This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. 1 PRC2 initiates gene silencing through the activity of histone deacetylase (HDAC), and histone methyltransferases that can methylate lysine 9 and 27 residues on histone H3 and lysine 26 on histone H1.2-6 The stable gene repression is then maintained by PRC1 through recognition of tri-methylated H3K27 (H3K27me3).3 The canonical repression pathway is initiated through trimethylation of H3K27 on the promoter of target gene by PRC2 subunit EZH1 or its paralog EZH2.2-4 The H3K27me3 mark is readily recognised by PRC1 through chromatin binding ability of its subunit CBX. The repression is further maintained through ubiquitination of lysine 119 residue on histone H2A (H2AK119ub) by RING1, a subunit of PRC1, or chromatin condensation. [7][8][9] Promoters of the polycomb target genes have been generally characterised as CpG-rich DNA sequences that are lacking other epigenetic markers.10-14 However, several other models of context depen...

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“…10-14 However, several other models of context dependent PRC2 recruitment mechanisms, including Polycomb response elements (PREs) 15-18 and ncRNAs [19][20][21][22] have been investigated.…”

Section: Compliance With Ethicsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Bmi1 – A Path to Targeting Cancer Stem Cells

Bakhshinyan¹,

Adile²,

Venugopal³

et al. 2017

European Oncology &Amp; Haematology

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“…The recent advances in technology as high-throughput sequencing (Gutschner and Diederichs 2012;Sana et al 2012;Karapetyan et al 2013) (ENCODE project) allowed the identification of a number of transcripts much higher than previously thought (Karapetyan et al 2013). Indeed the coding RNA (mRNAs) only represents 1-2 % of the genome sequences, and it is known that a much larger part of the genomes is actively transcribed, namely, in non-coding RNAs (ncRNAs) (Gutschner and Diederichs 2012;Deng and Sui 2013;Hauptman and Glavac 2013;Karapetyan et al 2013).…”

Section: Introductionmentioning

confidence: 98%

Satellite non-coding RNAs: the emerging players in cells, cellular pathways and cancer

et al. 2015

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For several decades, transcriptional inactivity was considered as one of the particular features of constitutive heterochromatin and, therefore, of its major component, satellite DNA sequences. However, more recently, succeeding evidences have demonstrated that these sequences can indeed be transcribed, yielding satellite non-coding RNAs with important roles in the organization and regulation of genomes. Since then, several studies have been conducted, trying to understand the function(s) of these sequences not only in the normal but also in cancer genomes. It is thought that the association between cancer and satncRNAs is mostly due to the influence of these transcripts in the genome instability, a hallmark of cancer. The few reports on satellite DNA transcription in cancer contexts point to its overexpression; however, this scenario may be far more complex, variable, and influenced by a number of factors and the exact role of satncRNAs in the oncogenic process remains poorly understood. The greater is the knowledge on the association of satncRNAs with cancer, the greater would be the opportunity to assist cancer treatment, either by the design of effective therapies targeting these molecules or by using them as biomarkers in cancer diagnosis, prognosis, and with predictive value.

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“…The transcriptional response to osmostress includes the induction and stabilization of hundreds of mRNAs (12)(13)(14) and the up-regulation of specific families of long noncoding RNAs (lncRNAs) (15), as well as a general down-regulation of gene expression (15)(16)(17)(18). Significantly, the latter class of RNA has been shown to induce chromatin remodeling and variations of nucleosome occupancy that have lasting effects on cellular memory and epigenetic makeup (21)(22)(23).…”

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confidence: 99%

Global Epitranscriptomics Profiling of RNA Post-Transcriptional Modifications as an Effective Tool for Investigating the Epitranscriptomics of Stress Response

Rose

Pazos

Curcio

et al. 2016

Molecular & Cellular Proteomics

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The simultaneous detection of all the post-transcriptional modifications (PTMs) that decorate cellular RNA can provide comprehensive information on the effects of changing environmental conditions on the entire epitranscriptome. To capture this type of information, we performed the analysis of ribonucleotide mixtures produced by hydrolysis of total RNA extracts from S. cerevisiae that was grown under hyperosmotic and heat shock conditions. Their global PTM profiles clearly indicated that the cellular responses to these types of stresses involved profound changes in the production of specific PTMs. The observed changes involved not only up-/down-regulation of typical PTMs, but also the outright induction of new ones that were absent under normal conditions, or the elimination of others that were normally present. Pointing toward the broad involvement of different classes of RNAs, many of the newly observed PTMs differed from those engaged in the known tRNA-based mechanism of translational recoding, which is induced by oxidative stress. Some of the expression effects were stress-specific, whereas others were not, thus suggesting that RNA PTMs may perform multifaceted activities in stress response, which are subjected to distinctive regulatory pathways. To explore their signaling networks, we implemented a strategy based on the systematic deletion of genes that connect established response genes with PTM biogenetic enzymes in a putative interactomic map. The results clearly identified PTMs that were under direct HOG control, a well-known protein kinase pathway involved in stress response in eukaryotes.

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Regulatory Roles for Long ncRNA and mRNA

Cited by 91 publications

References 185 publications

Bmi1 – A Path to Targeting Cancer Stem Cells

Bmi1 – A Path to Targeting Cancer Stem Cells

Satellite non-coding RNAs: the emerging players in cells, cellular pathways and cancer

Global Epitranscriptomics Profiling of RNA Post-Transcriptional Modifications as an Effective Tool for Investigating the Epitranscriptomics of Stress Response

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