Targeting post-translational histone modifying enzymes in glioblastoma

Kunadis, Elena; Lakiotaki, Eleftheria; Korkolopoulou, Penelope; Piperi, Christina

doi:10.1016/j.pharmthera.2020.107721

Cited by 70 publications

(46 citation statements)

References 200 publications

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“…HDACi can inhibit DNA repair responses and induce apoptosis, which contributes to enhanced sensitivity of tumor cells to chemotherapy and radiotherapy [ 32 ]. SAHA, for example, has been demonstrated to limit GBM development by reducing PRC2 function by decreasing EZH2 expression [ 33 ]. Furthermore, the application of SAHA suppressed c-Myc protein levels and extended animal survival in a patient-derived xenograft model [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma

Zhou

Liu

Wang

et al. 2021

IJMS

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Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Radiotherapy has long been an important treatment method of GBM. However, the intrinsic radioresistance of GBM cells is a key reason of poor therapeutic efficiency. Recently, many studies have shown that using the histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) in radiotherapy may improve the prognosis of GBM patients, but the underlying molecular mechanisms remain unclear. In this study, Gene Expression Omnibus (GEO) datasets GSE153982 and GSE131956 were analyzed to evaluate radiation-induced changes of gene expression in GBM without or with SAHA treatment, respectively. Additionally, the survival-associated genes of GBM patients were screened using the Chinese Glioma Genome Atlas (CGGA) database. Taking the intersection of these three datasets, 11 survival-associated genes were discovered to be activated by irradiation and regulated by SAHA. The expressions of these genes were further verified in human GBM cell lines U251, T98G, and U251 homologous radioresistant cells (U251R) by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). It was found that MMP14 mRNA was considerably highly expressed in the radioresistant cell lines and was reduced by SAHA treatment. Transfection of MMP14 siRNA (siMMP14) suppressed cell survivals of these GBM cells after irradiation. Taken together, our results reveal for the first time that the MMP14 gene contributed to SAHA-induced radiosensitization of GBM.

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Section: Discussionmentioning

confidence: 99%

MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma

Zhou

Liu

Wang

et al. 2021

IJMS

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“…Changes in expression of genes coding for lysine and arginine methyltransferases including G9a play a role in GBM pathogenesis [38]. An immunohistochemical study aimed at investigating G9a, H3K9me2 and histone H3K9me1 in human glioma and adjacent non-neoplastic tissue samples found that 86% (43 of 50) are positive for G9a expression, compared to 42% (21 of 50 samples) in non-neoplastic tissues.…”

Section: G9a and Gliomamentioning

confidence: 99%

EHMT2/G9a as an Epigenetic Target in Pediatric and Adult Brain Tumors

Souza

Freire

Jaeger

et al. 2021

IJMS

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Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also discuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors.

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“…Changes in expression of genes coding for lysine and arginine methyltransferases including G9a play a role in GBM pathogenesis [25]. An immunohistochemical study aimed at investigating G9a, H3K9me2 and histone H3K9me1 in human glioma and adjacent non-neoplastic tissue samples found that 86% (43 of 50) were positive for G9a expression, compared to 42% (21 of 50 samples) in non-neoplastic tissues.…”

Section: G9a and Gliomamentioning

confidence: 99%

EHMT2/G9a as an Epigenetic Target in Pediatric and Adult Brain Tumors

Souza¹,

Freire²,

Jaeger³

et al. 2021

Preprint

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Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development, and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), regulates changes in gene expression involved in embryonic development and differentiation of normal tissues. Overexpression of G9a has been observed in in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma multiforme (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. G9a inhibition dose-dependently reduces the viability of MB cells. Transcriptional levels of G9a are higher in MB tumors belonging to the SHH, Group 3, and Group 4, compared to Wnt tumors, and higher G9a gene expression may be a predictor of poor prognosis in patients with MB.

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Targeting post-translational histone modifying enzymes in glioblastoma

Cited by 70 publications

References 200 publications

MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma

MMP14 Contributes to HDAC Inhibition-Induced Radiosensitization of Glioblastoma

EHMT2/G9a as an Epigenetic Target in Pediatric and Adult Brain Tumors

EHMT2/G9a as an Epigenetic Target in Pediatric and Adult Brain Tumors

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