About: EGFR-vIII downregulated H2AZK4/7AC though the PI3K/AKT-HDAC2 axis to regulate cell cycle progression

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About: EGFR-vIII downregulated H2AZK4/7AC though the PI3K/AKT-HDAC2 axis to regulate cell cycle progression Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	EGFR-vIII downregulated H2AZK4/7AC though the PI3K/AKT-HDAC2 axis to regulate cell cycle progression
Creator	Wang, Lin Yang, Chao Zhao, Hongyu Zeng, Liang Wang, Yunfei Li, Yansheng Zhou, Junhu Kang, Chunsheng Shi, Jin Yi, Kaikai Wang, Qixue
Source	PMC
abstract	BACKGROUND: The EGFR-vIII mutation is the most common malignant event in GBM. Epigenetic reprogramming in EGFR-activated GBM has recently been suggested to downregulate the expression of tumour suppressor genes. Histone acetylation is important for chromatin structure and function. However, the role and biological function of H2AZK4/7AC in tumours have not yet been clarified. RESULTS: In our study, we found that EGFR-vIII negatively regulated H2AZK4/7AC expression though the PI3K/AKT-HDAC2 axis. Because HDAC1 and HDAC2 are highly homologous enzymes that usually form multi-protein complexes for transcriptional regulation and epigenetic landscaping, we simultaneously knocked out HDAC1 and HDAC2 and found that H2AZK4/7AC and H3K27AC were upregulated, which partially released EGFR-vIII-mediated inhibition of USP11, negative regulator of cell cycle. In addition, we demonstrated in vitro and in vivo that FK228 induced G1/S transition arrest in GBM with EGFR-vIII mutation. FK228 could enhance anti-tumour activity by upregulating expression of the tumour suppressor USP11 in GBM cells. CONCLUSIONS: EGFR-vIII mutation downregulates H2AZK4/7AC and H3K27AC, inhibiting USP11 expression though the PI3K/AKT-HDAC1/2 axis. FK228 is an effective and promising treatment for GBM with EGFR-vIII mutation.
has issue date	2020-01-28(xsd:dateTime)
bibo:doi	10.1186/s40169-020-0260-7
has license	cc-by
sha1sum (hex)	1522b124ad3b033cddc20307a8227e9ea205177c
schema:url	https://doi.org/10.1186/s40169-020-0260-7
resource representing a document's title	EGFR-vIII downregulated H2AZK4/7AC though the PI3K/AKT-HDAC2 axis to regulate cell cycle progression
has PubMed Central identifier	PMC6987283
schema:publication	Clin Transl Med
resource representing a document's body	covid:1522b124ad3b033cddc20307a8227e9ea205177c#body_text
is schema:about of	named entity 'H2AZ' named entity 'primary antibodies' named entity 'Immunofluorescence' named entity 'cell cycle' named entity 'U87' named entity 'GAPDH' named entity 'Cluster analysis' named entity 'HDAC1' named entity 'HDAC2' named entity 'lysate' named entity 'stereotactically' named entity 'EGFR' named entity 'H2AZ' named entity 'HDAC2' named entity 'EGFR' named entity 'angiogenesis' named entity 'chromatin' named entity 'Cyclin D1' named entity 'transcription factors' named entity 'CYFIP2' named entity 'CDK6' named entity 'upregulate' named entity 'U251' named entity 'U87' named entity 'GBM' named entity 'HDAC2' named entity 'histone' named entity 'staining' named entity 'USP11' named entity 'acute myeloid leukaemia' named entity 'staining' named entity 'tumour' named entity 'statistical significance' named entity 'GBM' named entity 'negatively regulated' named entity 'SELK' named entity 'HDAC' named entity 'FK228' named entity 'RT-qPCR' named entity 'Western blotting' named entity 'HDACs' named entity 'trimethylation' named entity 'PI3K/AKT pathway' named entity 'GBM' named entity 'tumour' named entity 'EGFR' named entity 'protein' named entity 'mutation' named entity 'primers' named entity 'acetylated' named entity 'HDAC2' named entity 'EGFR' named entity 'brain tumour' named entity 'primers' named entity 'cancer cells' named entity 'USP11' named entity 'HDAC1' named entity 'lysine' named entity 'H2AZ' named entity 'FK228' named entity 'mRNA' named entity 'Western blotting' named entity 'H3K4me3' named entity 'therapeutic targets' named entity 'HDAC2' named entity 'endogenous' named entity 'squamous cell carcinomas' named entity 'gastric cancer' named entity 'U251' named entity 'siRNA' named entity 'GBM' named entity 'EGFR' named entity 'HDAC2'

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