GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcription

Abstract Background The GATAD1 gene overexpression induced by GATAD1 amplification upregulation is detected in different human tumors. To date, the relationship between GATAD1 amplification and glioma oncogenesis and malignancy is still unknown. Methods GATAD1 gene amplification and expression were...

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Main Authors: Shanshan Zhang, Min Gao, Lin Yu
Format: Article
Language:English
Published: Wiley 2019-09-01
Series:Cancer Medicine
Subjects:
Online Access:https://doi.org/10.1002/cam4.2405
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author Shanshan Zhang
Min Gao
Lin Yu
author_facet Shanshan Zhang
Min Gao
Lin Yu
author_sort Shanshan Zhang
collection DOAJ
description Abstract Background The GATAD1 gene overexpression induced by GATAD1 amplification upregulation is detected in different human tumors. To date, the relationship between GATAD1 amplification and glioma oncogenesis and malignancy is still unknown. Methods GATAD1 gene amplification and expression were analyzed in 187 gliomas using qPCR and immunostaining. The relation of GATAD1 to patients’ prognoses was assessed via the Kaplan–Meier method. The MTT and orthotopic tumor transplantation assays were used to identify the function of GATAD1 in glioma proliferation. cDNA microarray, ChIP qPCR, EMSA and 3C were used to screen the downstream mechanism of GATAD1 regulating glioma proliferation. Results Our results indicated that GATAD1 gene amplification and GATAD1 gene expression are novel independent diagnosis biomarkers to indicate poor outcome of glioma patients. GATAD1 knockdown can remarkably suppress GBM cell proliferation both in vitro and in vivo. GATAD1 could promote CCND1 gene transcription by inducing long range chromatin architectural interaction on the CCND1 promoter. Then GATAD1 sequentially accelerates GBM cell cycle transition and proliferation via regulating CCND1. Conclusions We identify GATAD1 as a novel potential diagnosis biomarker and promising prognosis predictor in glioma patients. Functionally, we confirm GATAD1 as an epigenetic chromatin topological regulator that promotes glioma proliferation by targeting CCND1.
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spelling doaj.art-11aa2303a242403983effaa6b3c1dd6e2022-12-21T23:04:47ZengWileyCancer Medicine2045-76342019-09-018115242525310.1002/cam4.2405GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcriptionShanshan Zhang0Min Gao1Lin Yu2Department of Radiology Tianjin Medical University General Hospital Tianjin ChinaDepartment of Biochemistry and Molecular Biology School of Basic Medical Sciences of Tianjin Medical University Tianjin ChinaDepartment of Biochemistry and Molecular Biology School of Basic Medical Sciences of Tianjin Medical University Tianjin ChinaAbstract Background The GATAD1 gene overexpression induced by GATAD1 amplification upregulation is detected in different human tumors. To date, the relationship between GATAD1 amplification and glioma oncogenesis and malignancy is still unknown. Methods GATAD1 gene amplification and expression were analyzed in 187 gliomas using qPCR and immunostaining. The relation of GATAD1 to patients’ prognoses was assessed via the Kaplan–Meier method. The MTT and orthotopic tumor transplantation assays were used to identify the function of GATAD1 in glioma proliferation. cDNA microarray, ChIP qPCR, EMSA and 3C were used to screen the downstream mechanism of GATAD1 regulating glioma proliferation. Results Our results indicated that GATAD1 gene amplification and GATAD1 gene expression are novel independent diagnosis biomarkers to indicate poor outcome of glioma patients. GATAD1 knockdown can remarkably suppress GBM cell proliferation both in vitro and in vivo. GATAD1 could promote CCND1 gene transcription by inducing long range chromatin architectural interaction on the CCND1 promoter. Then GATAD1 sequentially accelerates GBM cell cycle transition and proliferation via regulating CCND1. Conclusions We identify GATAD1 as a novel potential diagnosis biomarker and promising prognosis predictor in glioma patients. Functionally, we confirm GATAD1 as an epigenetic chromatin topological regulator that promotes glioma proliferation by targeting CCND1.https://doi.org/10.1002/cam4.2405chromatin architectural interactionGATAD1gene amplificationgliomaprognosis biomarker
spellingShingle Shanshan Zhang
Min Gao
Lin Yu
GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcription
Cancer Medicine
chromatin architectural interaction
GATAD1
gene amplification
glioma
prognosis biomarker
title GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcription
title_full GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcription
title_fullStr GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcription
title_full_unstemmed GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcription
title_short GATAD1 gene amplification promotes glioma malignancy by directly regulating CCND1 transcription
title_sort gatad1 gene amplification promotes glioma malignancy by directly regulating ccnd1 transcription
topic chromatin architectural interaction
GATAD1
gene amplification
glioma
prognosis biomarker
url https://doi.org/10.1002/cam4.2405
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AT linyu gatad1geneamplificationpromotesgliomamalignancybydirectlyregulatingccnd1transcription