Publications by authors named "Sadhan Majumder"

The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of four opioid receptor genes (Oprm1, Oprd1, Oprl1 and Oprk1) and the cannabinoid CB1 receptor (Cnr1) gene in the DRG regulate nociception.

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The transcription repressor REST in the dorsal root ganglion (DRG) is upregulated by peripheral nerve injury and promotes the development of chronic pain. However, the genes targeted by REST in neuropathic pain development remain unclear. The expression levels of 4 opioid receptor (Oprm1, Oprd1, Oprl1, Oprk1) and the cannabinoid CB1 receptor (Cnr1) genes in the DRG regulate nociception.

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Background: Glioblastoma (GBM) is a lethal, heterogeneous human brain tumor, with regulatory mechanisms that have yet to be fully characterized. Previous studies have indicated that the transcriptional repressor REST (repressor element-1 silencing transcription factor) regulates the oncogenic potential of GBM stem cells (GSCs) based on level of expression. However, how REST performs its regulatory role is not well understood.

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Overexpression of REST has been implicated in brain tumors, ischemic insults, epilepsy, and movement disorders such as Huntington's disease. However, owing to the lack of a conditional REST overexpression animal model, the mechanism of action of REST overexpression in these disorders has not been established in vivo. We created a REST overexpression mouse model using the human REST (hREST) gene.

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The dynamic and reversible N-methyladenosine (mA) RNA modification installed and erased by N-methyltransferases and demethylases regulates gene expression and cell fate. We show that the mA demethylase ALKBH5 is highly expressed in glioblastoma stem-like cells (GSCs). Silencing ALKBH5 suppresses the proliferation of patient-derived GSCs.

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Background: Glioblastoma (GBM) is one of the most common, aggressive, and invasive human brain tumors. There are few reliable mechanism-based therapeutic approaches for GBM patients. The transcriptional repressor RE1 silencing transcriptional factor (REST) regulates the oncogenic properties of a class of GBM stem-like cells (high-REST [HR]-GSCs) in humans.

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Unlabelled: Glioblastoma (GBM) is the most aggressive human brain tumor. Although several molecular subtypes of GBM are recognized, a robust molecular prognostic marker has yet to be identified. Here, we report that the stemness regulator Sox2 is a new, clinically important target of microRNA-21 (miR-21) in GBM, with implications for prognosis.

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Background: Cancer stem cells (CSCs) provide an additional layer of complexity for tumor models and targets for therapeutic development. The balance between CSC self-renewal and differentiation is driven by niche components including adhesion, which is a hallmark of stemness. While studies have demonstrated that the reduction of adhesion molecules, such as integrins and junctional adhesion molecule-A (JAM-A), decreases CSC maintenance.

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Our previous studies have shown that the regulatory network that maintains pluripotency in mouse embryonic stem cells (mESCs) is regulated in a context-dependent manner and can be modulated, at least in part, by re-calibration of an intracellular network of pluripotency factors as well as cues arising from the extracellular matrix. The transcriptional repressor REST represses miR-21 and, thus, regulates self-renewal in E14Tg2a.4 mESCs cultured in the absence of mouse embryonic fibroblast feeder cell effects.

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Article Synopsis
  • Nuclear β-catenin can cause different types of cancer when it’s overactive, but we don't know what happens to it.
  • A protein called TRIM33 helps break down this β-catenin in the nucleus, reducing its levels, which can slow down tumors.
  • TRIM33 may be important for future cancer treatments because it acts like a "tumor fighter" by making sure β-catenin doesn’t stay around too long in cancer cells.
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Pyruvate kinase M2 (PKM2) is expressed at high levels during embryonic development and tumour progression and is important for cell growth. However, it is not known whether it directly controls cell division. Here, we found that Aurora B phosphorylates PKM2, but not PKM1, at T45; this phosphorylation is required for PKM2's localization and interaction with myosin light chain 2 (MLC2) in the contractile ring region of mitotic cells during cytokinesis.

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Background: REST is abundantly expressed in mouse embryonic stem cells (ESCs). Many genome-wide analyses have found REST to be an integral part of the ESC pluripotency network. However, experimental systems have produced contradictory findings: (1) REST is required for the maintenance of ESC pluripotency and loss of REST causes increased expression of differentiation markers, (2) REST is not required for the maintenance of ESC pluripotency and loss of REST does not change expression of differentiation markers, and (3) REST is not required for the maintenance of ESC pluripotency but loss of REST causes decreased expression of differentiation markers.

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Background: Several studies have established Glioblastoma Multiforme (GBM) prognostic and predictive models based on age and Karnofsky Performance Status (KPS), while very few studies evaluated the prognostic and predictive significance of preoperative MR-imaging. However, to date, there is no simple preoperative GBM classification that also correlates with a highly prognostic genomic signature. Thus, we present for the first time a biologically relevant, and clinically applicable tumor Volume, patient Age, and KPS (VAK) GBM classification that can easily and non-invasively be determined upon patient admission.

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Glioblastoma multiforme (GBM) tumors are the most common malignant primary brain tumors in adults. Although many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs), the mechanisms that regulate self-renewal and other oncogenic properties of GSCs are only now being unraveled. Here we showed that GSCs derived from GBM patient specimens express varying levels of the transcriptional repressor repressor element 1 silencing transcription factor (REST), suggesting heterogeneity across different GSC lines.

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Background: Despite recent discoveries of new molecular targets and pathways, the search for an effective therapy for Glioblastoma Multiforme (GBM) continues. A newly emerged field, radiogenomics, links gene expression profiles with MRI phenotypes. MRI-FLAIR is a noninvasive diagnostic modality and was previously found to correlate with cellular invasion in GBM.

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Production of neurons from non-neural cells has far-reaching clinical significance. We previously found that myoblasts can be converted to a physiologically active neuronal phenotype by transferring a single recombinant transcription factor, REST-VP16, which directly activates target genes of the transcriptional repressor, REST. However, the neuronal subtype of M-RV cells and whether they can establish synaptic communication in the brain have remained unknown.

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The neuronal repressor REST (RE1-silencing transcription factor; also called NRSF) is expressed at high levels in mouse embryonic stem (ES) cells, but its role in these cells is unclear. Here we show that REST maintains self-renewal and pluripotency in mouse ES cells through suppression of the microRNA miR-21. We found that, as with known self-renewal markers, the level of REST expression is much higher in self-renewing mouse ES cells than in differentiating mouse ES (embryoid body, EB) cells.

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The repressor element 1 (RE-1)-silencing transcription factor (REST), also known as the neuron-restrictive silencer factor (NRSF), was originally discovered as a transcriptional repressor of a large number of primarily terminal neuronal differentiation genes in nonneuronal cells and neural stem cells (NSCs). Although REST is expressed in NSCs, its transcription is generally blocked as NSCs undergo differentiation, and it is rarely expressed in terminally differentiated neurons. In support of its function as a transcriptional repressor, REST was found to contain a DNA-binding domain and two repressor domains.

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Medulloblastoma, one of the most malignant brain tumors in children, is thought to arise from undifferentiated neural stem/progenitor cells (NSCs) present in the external granule layer of the cerebellum. However, the mechanism of tumorigenesis remains unknown for the majority of medulloblastomas. In this study, we found that many human medulloblastomas express significantly elevated levels of both myc oncogenes, regulators of neural progenitor proliferation, and REST/NRSF, a transcriptional repressor of neuronal differentiation genes.

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Medulloblastoma, one of the most malignant pediatric brain tumors, is believed to arise from the undifferentiated external granule-layer cells in the cerebellum. It is a heterogeneous cancer, and the mechanism of tumorigenesis for the majority of types is unknown. Repressor element-1 silencing transcription/neuron-restrictive silencer factor (REST/NRSF) is a transcriptional repressor that can block transcription of a battery of neuronal differentiation genes by binding to a specific consensus DNA sequence present in their regulatory region.

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REST/NRSF is a transcriptional repressor that acts at the terminal stage of the neuronal differentiation pathway and blocks the transcription of several differentiation genes. REST/NRSF is generally downregulated during induction of neuronal differentiation. The recombinant transcription factor REST-VP16 binds to the same DNA binding site as does REST/NRSF but functions as an activator instead of a repressor and can directly activate the transcription of REST/NRSF target genes.

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Repressor element 1 (RE1)-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) can repress several terminal neuronal differentiation genes by binding to a specific DNA sequence (RE1/neuron-restrictive silencer element [NRSE]) present in their regulatory regions. REST-VP16 binds to the same RE1/NRSE, but activates these REST/NRSF target genes. However, it is unclear whether REST-VP16 expression is sufficient to cause formation of functional neurons either from neural stem cells or from heterologous stem cells.

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