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Publication

Transgelin Promotes Glioblastoma Stem Cell Hypoxic Responses and Maintenance Through p53 Acetylation.

Advanced science (Weinheim, Baden-Wurttemberg, Germany) | 2023

Glioblastoma (GBM) is a lethal cancer characterized by hypervascularity and necrosis associated with hypoxia. Here, it is found that hypoxia preferentially induces the actin-binding protein, Transgelin (TAGLN), in GBM stem cells (GSCs). Mechanistically, TAGLN regulates HIF1α transcription and stabilizes HDAC2 to deacetylate p53 and maintain GSC self-renewal. To translate these findings into preclinical therapeutic paradigm, it is found that sodium valproate (VPA) is a specific inhibitor of TAGLN/HDAC2 function, with augmented efficacy when combined with natural borneol (NB) in vivo. Thus, TAGLN promotes cancer stem cell survival in hypoxia and informs a novel therapeutic paradigm.

Pubmed ID: 38087889 RIS Download

Research resources used in this publication

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Antibodies used in this publication

Associated grants

Agency: HUST Academic Frontier Youth Team,
Agency: Anhui Provincial Natural Science Foundation,
Id: 2108085J43
Agency: Natural Science Foundation of Hubei Province,
Id: 2020CFB678
Agency: National Natural Science Foundation of China,
Id: 82072805
Agency: Huazhong University of Science and Technology,
Id: 2019kfyXJJS187

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This is a list of tools and resources that we have found mentioned in this publication.

Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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SAMTOOLS (tool)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

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JASPAR (tool)

RRID:SCR_003030

Open source database of curated, non-redundant set of profiles derived from published collections of experimentally defined transcription factor binding sites for multicellular eukaryotes. Consists of open data access, non-redundancy and quality. JASPAR CORE is smaller set that is non-redundant and curated. Collection of transcription factor DNA-binding preferences, modeled as matrices. These can be converted into Position Weight Matrices (PWMs or PSSMs), used for scanning genomic sequences. Web interface for browsing, searching and subset selection, online sequence analysis utility and suite of programming tools for genome-wide and comparative genomic analysis of regulatory regions. New functions include clustering of matrix models by similarity, generation of random matrices by sampling from selected sets of existing models and a language-independent Web Service applications programming interface for matrix retrieval.

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Ivy Glioblastoma Atlas Project (tool)

RRID:SCR_005044

Platform for exploring the anatomic and genetic basis of glioblastoma at the cellular and molecular levels that includes two interactive databases linked together by de-identified tumor specimen numbers to facilitate comparisons across data modalities: * The open public image database, here, providing in situ hybridization data mapping gene expression across the anatomic structures inherent in glioblastoma, as well as associated histological data suitable for neuropathological examination * A companion database (Ivy GAP Clinical and Genomic Database) offering detailed clinical, genomic, and expression array data sets that are designed to elucidate the pathways involved in glioblastoma development and progression. This database requires registration for access. The hope is that researchers all over the world will mine these data and identify trends, correlations, and interesting leads for further studies with significant translational and clinical outcomes. The Ivy Glioblastoma Atlas Project is a collaborative partnership between the Ben and Catherine Ivy Foundation, the Allen Institute for Brain Science and the Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment.

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UCSC Genome Browser (tool)

RRID:SCR_005780

Portal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.

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PrimerBank (tool)

RRID:SCR_006898

Database of human and mouse primer pairs for gene expression analysis by polymerase chain reaction (PCR) and quantitative PCR (qPCR). A total of 306,800 primers covering most known human and mouse genes can be accessed from the PrimerBank database, together with information on these primers such as T(m), location on the transcript and amplicon size. For each gene, at least one primer pair has been designed and in many cases alternative primer pairs exist. Primers have been designed to work under the same PCR conditions, thus facilitating high-throughput QPCR. All primers in PrimerBank were carefully designed to ensure gene specificity. All experimental validation data for mouse primers are available from PrimerBank. You can submit your primers. They will be added to the database once they are properly QCd.

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Millipore (tool)

RRID:SCR_008983

An Antibody supplier

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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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cutadapt (tool)

RRID:SCR_011841

Software tool that removes adapter sequences from DNA sequencing reads.

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Trimmomatic (tool)

RRID:SCR_011848

Software Java pipeline for trimming tasks for Illumina paired end and single ended data. Flexible Trimmer for Illumina Sequence Data. Pair aware preprocessing tool optimized for Illumina next generation sequencing data. Includes several processing steps for read trimming and filtering. Operating systems Unix/Linux, Mac OS, Windows.

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Genomic Data Commons Data Portal (GDC Data Portal) (tool)

RRID:SCR_014514

A unified data repository of the National Cancer Institute (NCI)'s Genomic Data Commons (GDC) that enables data sharing across cancer genomic studies in support of precision medicine. The GDC supports several cancer genome programs at the NCI Center for Cancer Genomics (CCG), including The Cancer Genome Atlas (TCGA), Therapeutically Applicable Research to Generate Effective Treatments (TARGET), and the Cancer Genome Characterization Initiative (CGCI). The GDC Data Portal provides a platform for efficiently querying and downloading high quality and complete data. The GDC also provides a GDC Data Transfer Tool and a GDC API for programmatic access.

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Thermo Xcalibur (tool)

RRID:SCR_014593

A software which acquires and processes data sets, primarily through the Xcalibur system.

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Chinese Glioma Genome Atlas (tool)

RRID:SCR_018802

Web application for data storage and analysis to explore brain tumors datasets from Chinese cohorts. Data portal for storage and interactive exploration of multi-dimensional functional genomic data that includes primary and recurrent glioma samples from Chinese cohorts. Allows users to browse DNA mutation profile, mRNA/microRNA expression profile and methylation profile, and to do correlation and survival analysis in specific glioma subtype.

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ELDA (tool)

RRID:SCR_018933

Software tool for limiting dilution analysis, with particular attention to needs of stem cell assays. Provides confidence intervals for all LDA data sets, including those with 0% or 100% responses. Other features include test of adequacy of single hit hypothesis, tests for frequency differences between multiple data sets, and ability to take advantage of cases where number of cells in sample is counted exactly.

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GlioVis (tool)

RRID:SCR_023877

Web application for data visualization and analysis to explore brain tumors expression datasets.

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GeneHancer (tool)

RRID:SCR_023953

Database of human regulatory elements like enhancers and promoters, and their inferred target genes which is embedded in GeneCards, human gene compendium. Associations between regulatory elements and target genes were based on multiple sources of linking molecular data, along with distance.

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