<scp>EZH</scp>
            2 cooperates with gain‐of‐function p53 mutants to promote cancer growth and metastasis

Zhao, Yu; Ding, Liya; Wang, Dejie; Ye, Zhenqing; He, Yundong; Ma, Linlin; Zhu, Runzhi; Pan, Yunqian; Wu, Qiang; Pang, Kun; Hou, Xiaonan; Weroha, S. John; Han, Conghui; Coleman, Roger; Coleman, Ilsa M.; Karnes, R.J.; Zhang, Jun; Nelson, Peter S.; Wang, Liguo; Huang, Haojie

doi:10.15252/embj.201899599

Cited by 64 publications

(36 citation statements)

References 80 publications

(133 reference statements)

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“…5 × 10 6 C4-2 cells treated with 100 µM 4-Thiouridine (4SU) for 8 h were washed with cold PBS one time and cells were irradiated once with 150 mJ/cm 2 at 365 nm using a Startalinker 38 . Cells were lysed in lysis buffer (50 mM Tris-HCL, pH 7.4, 100 mM NaCl, 1% NP-40, 0.1% SDS, 0.5% sodium deoxycholate, protease inhibitor cooktail and RNase inhibitors) with protease inhibitors (1 mL) and transferred to 1.5 mL microtubes.…”

Section: Methodsmentioning

confidence: 99%

“…Cell invasion assay in vitro was performed with Corning matrigel invasion chamber assay according to manufacturer's instructions as previously described 38 . Briefly, cells were diluted to 3 × 10 4 cells per well in serum-free medium and plated to the inside of matrigel chamber in 24-well plates, outside the chamber was added the medium with 10% FBS.…”

Section: Methodsmentioning

confidence: 99%

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Functional roles of antisense enhancer RNA for promoting prostate cancer progression

et al. 2021

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Functional roles of antisense enhancer RNA for promoting prostate cancer progression

et al. 2021

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“…Provocatively, it was recently reported that EZH2 directly binds to the internal ribosome entry site (IRES) on the mRNAs of both wild-type and mutated p53, leading to enhanced translation of p53 protein, especially mutant one, and subsequently promoted cancer growth and metastasis. However, this EZH2-RNA interaction seems to be independent of EZH2's methyltransferase activity (Zhao et al, 2019). These studies present a diverse and complex picture of EZH2 functions in regulation of DDR.…”

Section: Introductionmentioning

confidence: 90%

A non-canonical EZH2 function sensitizes solid tumors to genotoxic stress

Liao

Chen

Shah

et al. 2020

Preprint

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SummaryDrugs that block the activity of the methyltransferase EZH2 are in clinical development for the treatment of non-Hodgkin lymphomas harboring gain-of-function EZH2 mutations that enhance its polycomb repressive function. In contrast, in castration-resistant prostate cancer (CRPC) we have previously reported that EZH2 plays a non-canonical role as a transcriptional activator. In this setting, we now show that EZH2 inhibitors can also block the non-canonical activity of EZH2 and inhibit the growth of CRPC cells. Gene expression and epigenomic profiling of cells treated with EZH2 inhibitors demonstrated that rather than de-repressing tumor suppressor genes silenced by PRC2, EZH2 inhibitors downregulate a set of DNA repair genes that are directly regulated by EZH2. In addition, genome-wide CRISPR/Cas9-mediated loss-of-function screens in the presence of EZH2 inhibitors identified these DNA repair genes to underlie the growth-inhibitory function of these compounds. Interrogation of public data from diverse solid tumor types expressing wild-type EZH2 showed that expression of DNA damage repair genes is significantly correlated with cellular sensitivity to EZH2 inhibitors. Consistent with these findings, treatment of CRPC cells with EZH2 inhibitors dramatically enhanced their sensitivity to genotoxic stress. These studies reveal a previously unappreciated mechanism of action of EZH2 inhibitors and provide a mechanistic basis for potential new combination cancer therapies.

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“…EZH2 gene is a member of the Polycomb-group (PcG) family, is a core subunit of the polycomb repressor complex 2 (PRC2), participates in the formation of multimeric protein complexes to maintain the transcriptional repressive state of genes over successive cell generations 12. EZH2 has abnormal expression in almost all malignant cancers 13-16.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-101-3p advances cisplatin sensitivity in bladder urothelial carcinoma through targeted silencing EZH2

Li¹,

Xie²,

Zhang³

2019

J. Cancer

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Objective : Chemotherapy is a major therapeutic method for bladder urothelial carcinoma (BUC), which can effectively improve the prognosis of BUC patients, but the chemoresistance often leads to chemotherapy failure. This study will research the regulatory roles and molecular mechanism of miR-101-3p in BUC chemoresistance. Materials and Methods : The quantitative real-time PCR was used to detect the expression of miRNA-101-3p and EZH2. The proliferation and chemoresistance were analyzed by CCK8 assay. Luciferase reporter assay was used to verify the combination between miR-101-3p and EZH2. Protein expression was detected by Western blotting. Flow cytometry was used to examine apoptosis rate. Results : The miR-101-3p expression was down-regulated in cisplatin (CDDP) resistant BUC cell line (T24/CDDP) and tissues, and was positively related to sensitivity of BUC to CDDP. In T24/CDDP cells, the up-regulation of miR-101-3p decreased the half maximal inhibitory concentration (IC50) to CDDP, depressed the expression of MRP1 protein, promote the CDDP-induced cytotoxicity, and advanced CDDP sensitivity. A series of in vitro experiments certified the EZH2 gene was a target gene of miR-101-3p, including luciferase reporter assay, western blotting and so on. Up-regulation of EZH2 largely reversed the regulatory effects of miR-101-3p enhancement on CDDP sensitivity in T24/CDDP cells. Conclusion : The expression of miR-101-3p is positively related to CDDP sensitivity of BUC, miR-101-3p advances sensitivity of BUC to CDDP through targeted silencing EZH2.

show abstract

EZH 2 cooperates with gain‐of‐function p53 mutants to promote cancer growth and metastasis

Cited by 64 publications

References 80 publications

Functional roles of antisense enhancer RNA for promoting prostate cancer progression

Functional roles of antisense enhancer RNA for promoting prostate cancer progression

A non-canonical EZH2 function sensitizes solid tumors to genotoxic stress

MicroRNA-101-3p advances cisplatin sensitivity in bladder urothelial carcinoma through targeted silencing EZH2

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