MYCN contributes to the malignant characteristics of erythroleukemia through EZH2-mediated epigenetic repression of p21

Liu, Li; Xu, Feng; Chang, Chunkang; He, Qi; Wu, Lingyun; Zhang, Zheng

doi:10.1038/cddis.2017.526

Cited by 18 publications

(11 citation statements)

References 47 publications

(59 reference statements)

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“…K562 was the most affected cell line, particularly when using sh PHF19 #2. Of note is that K562 cell growth reduction upon EZH2 depletion using shRNAs has been reported, but accompanied by an increased apoptotic rate ( Xie et al, 2016 ; Liu et al, 2017 ). Hence, we decided to profile the cell cycle by propidium iodide staining.…”

Section: Resultsmentioning

confidence: 97%

Polycomb Factor PHF19 Controls Cell Growth and Differentiation Toward Erythroid Pathway in Chronic Myeloid Leukemia Cells

García-Montolio

Ballaré

Blanco

et al. 2021

Front. Cell Dev. Biol.

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Polycomb group (PcG) of proteins are a group of highly conserved epigenetic regulators involved in many biological functions, such as embryonic development, cell proliferation, and adult stem cell determination. PHD finger protein 19 (PHF19) is an associated factor of Polycomb repressor complex 2 (PRC2), often upregulated in human cancers. In particular, myeloid leukemia cell lines show increased levels of PHF19, yet little is known about its function. Here, we have characterized the role of PHF19 in myeloid leukemia cells. We demonstrated that PHF19 depletion decreases cell proliferation and promotes chronic myeloid leukemia (CML) differentiation. Mechanistically, we have shown how PHF19 regulates the proliferation of CML through a direct regulation of the cell cycle inhibitor p21. Furthermore, we observed that MTF2, a PHF19 homolog, partially compensates for PHF19 depletion in a subset of target genes, instructing specific erythroid differentiation. Taken together, our results show that PHF19 is a key transcriptional regulator for cell fate determination and could be a potential therapeutic target for myeloid leukemia treatment.

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Section: Resultsmentioning

confidence: 97%

Polycomb Factor PHF19 Controls Cell Growth and Differentiation Toward Erythroid Pathway in Chronic Myeloid Leukemia Cells

García-Montolio

Ballaré

Blanco

et al. 2021

Front. Cell Dev. Biol.

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“…While EZH2 is a well-known tumorigenic factor and therapeutic target for neuroblastoma, EZH2 is likely to exert tumorigenic functions through both RNA-binding-dependent and -independent pathways. EZH2 is described as an MYCN transcriptional target in erythroleukemia, and the aurora kinase inhibitor MLN8237 was used in this context to repress the MYCN-EZH2 axis [68]. Currently, the EZH2 inhibitor tazemetostat is under clinical evaluation for use in recurrent neuroblastoma (Phase II, Clinical Trials Identifier: NCT03213665).…”

Section: Other Reported Mycn-associated Rbps: Nono Igf2bp1 Igf2bp3mentioning

confidence: 99%

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Bell

Hagemann

Holien

et al. 2020

IJMS

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Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have reported roles in neuroblastoma development and patient outcome, the role of RBPs in neuroblastoma is relatively unstudied. In order to elucidate novel RBPs involved in MYCN-amplified and other high-risk neuroblastoma subtypes, we performed differential mRNA expression analysis of RBPs in a large primary tumour cohort (n = 498). Additionally, we found via Kaplan–Meier scanning analysis that 685 of the 1483 tested RBPs have prognostic value in neuroblastoma. For the top putative oncogenic candidates, we analysed their expression in neuroblastoma cell lines, as well as summarised their characteristics and existence of chemical inhibitors. Moreover, to help explain their association with neuroblastoma subtypes, we reviewed candidate RBPs’ potential as biomarkers, and their mechanistic roles in neuronal and cancer contexts. We found several highly significant RBPs including RPL22L1, RNASEH2A, PTRH2, MRPL11 and AFF2, which remain uncharacterised in neuroblastoma. Although not all RBPs appear suitable for drug design, or carry prognostic significance, we show that several RBPs have strong rationale for inhibition and mechanistic studies, representing an alternative, but nonetheless promising therapeutic strategy in neuroblastoma treatment.

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“…SETD2 can interact with p53 to regulate the transcription of its target genes encoding for e.g. p21 cip1/waf1 , Fas, and Puma [95]. SETD2 loss could also promote tumor growth in a p53-independent manner, leading to aberrant mitosis and multinucleated giant cells in tumors.…”

Section: Epigenetic Regulation Of P21cip1/waf1mentioning

confidence: 99%

Epigenetic Regulation of p21cip1/waf1 in Human Cancer

Ocker

Bitar

Monteiro

et al. 2019

Cancers

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p21cip1/waf1 is a central regulator of cell cycle control and survival. While mutations are rare, it is commonly dysregulated in several human cancers due to epigenetic mechanisms influencing its transcriptional control. These mechanisms include promoter hypermethylation as well as additional pathways such as histone acetylation or methylation. The epigenetic regulators include writers, such as DNA methyltransferases (DNMTs); histone acetyltransferases (HATs) and histone lysine methyltransferases; erasers, such as histone deacetylases (HDACs); histone lysine demethylases [e.g., the Lysine Demethylase (KDM) family]; DNA hydroxylases; readers, such as the methyl-CpG-binding proteins (MBPs); and bromodomain-containing proteins, including the bromo- and extraterminal domain (BET) family. We further discuss the roles that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play in the epigenetic control of p21cip1/waf1 expression and its function in human cancers.

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MYCN contributes to the malignant characteristics of erythroleukemia through EZH2-mediated epigenetic repression of p21

Cited by 18 publications

References 47 publications

Polycomb Factor PHF19 Controls Cell Growth and Differentiation Toward Erythroid Pathway in Chronic Myeloid Leukemia Cells

Polycomb Factor PHF19 Controls Cell Growth and Differentiation Toward Erythroid Pathway in Chronic Myeloid Leukemia Cells

Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma

Epigenetic Regulation of p21cip1/waf1 in Human Cancer

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