Role of Enhancer of Zeste Homolog 2 Polycomb Protein and Its Significance in Tumor Progression and Cell Differentiation

Marchesi, Irene; Bagella, Luigi

doi:10.5772/55370

Cited by 8 publications

(21 citation statements)

References 214 publications

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“…Our recent transcriptome study identified miR‐101a‐3p as one of the most abundant miRNAs in the amygdala and showed that HR rats had significantly lower miR‐101a‐3p levels in the amygdala relative to LRs (Cohen et al ., ). A major target miR‐101a‐3p is the polycomb repressive complex 2 (PRC2), a multiprotein complex including histone methyltransferase enhancer of zeste homolog 2 (Ezh2; Varambally et al ., ; Friedman et al ., ), which mediates gene silencing via trimethylation of histone 3 at lysine 27 (H3K27me3; Cao et al ., ; Marchesi & Bagella, ). PRC2 critically regulates gene expression during several developmental processes (Marchesi et al ., ), including formation of brain circuits (Di Meglio et al ., ; Neo et al ., ), although a fairly limited number of studies have examined Ezh2 and H3K27me3 in the adult brain (Qi et al ., ; Zhang et al ., ; Koo et al ., ).…”

Section: Introductionmentioning

confidence: 98%

Amygdalar expression of the microRNA miR‐101a and its target Ezh2 contribute to rodent anxiety‐like behaviour

Cohen

Jackson

Ballestas

et al. 2017

Eur J of Neuroscience

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A greater understanding of neural mechanisms that contribute to anxiety is needed in order to develop better therapeutic interventions. The current study interrogates a novel molecular mechanism that shapes anxiety-like behavior, demonstrating that the microRNA miR-101a-3p and its target, enhancer of zeste homolog 2 (Ezh2) in the amygdala, contribute to rodent anxiety-like behavior. We utilized rats that were selectively-bred for differences in emotionality and stress reactivity, showing that high novelty responding (HR) rats, which display low trait anxiety, have lower miR-101a-3p levels in the amygdala compared to low novelty responding (LR) rats that characteristically display high trait anxiety. To determine if there is a causal relationship between amygdalar miR-101a-3p and anxiety behavior, we used a viral approach to over-express miR-101a-3p in the amygdala of HR rats and test whether it would increase their typically low levels of anxiety-like behavior. We found that increasing miR-101a-3p in the amygdala increased HRs’ anxiety-like behavior in the open field test and elevated plus maze. Viral-mediated miR-101a-3p over-expression also reduced expression of the histone methyltransferase Ezh2, which mediates gene silencing via tri-methylation of histone 3 at lysine 27 (H3K27me3). Knockdown of Ezh2 with short-interfering RNA (siRNA) also increased HRs’ anxiety-like behavior, but to a lesser degree than miR-101a-3p over-expression. Overall our data demonstrate that increasing miR-101a-3p expression in the amygdala increases anxiety-like behavior and that this effect is at least partially mediated via repression of Ezh2. This work adds to the growing body of evidence implicating miRNAs and epigenetic regulation as molecular mediators of anxiety behavior.

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Section: Introductionmentioning

confidence: 98%

Amygdalar expression of the microRNA miR‐101a and its target Ezh2 contribute to rodent anxiety‐like behaviour

Cohen

Jackson

Ballestas

et al. 2017

Eur J of Neuroscience

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“…In addition, EZH2 expression is generally correlated with metastatic cancer cells and poor prognosis. 6,12,107 It has been proposed that the role of EZH2 in cancer is linked to its activity in self-renewal promotion and in the maintenance of undifferentiated state of cells. EZH2 target genes are generally tumor suppressor and differentiation genes, and its deregulation promotes cancer progression.…”

Section: Ezh2 Interplay Between Differentiation and Cancermentioning

confidence: 99%

“…Several studies showed the role of PRC2 as regulator of gene expression during organogenesis (reviewed in ref. 6). …”

Section: Ezh2 Interplay Between Differentiation and Cancermentioning

confidence: 99%

“…Once cells complete the differentiation process, they irreversibly become adult somatic cells with specific functional and morphological features. 6 Chromatin changes have been also associated with pathological processes, such as cancer; cancer epigenetics is a branch of the epigenetic field, focusing on the abnormalities of the epigenetic processes that are likely to be involved in carcinogenesis and/or tumor progression. 2,5,7,8 For instance, it is now well established that CpG DNA hypermethylation characterizes the promoter region of numerous tumor suppressor genes in cancer cells, inducing transcriptional repression and promoting cancer progression.…”

Section: Introductionmentioning

confidence: 99%

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Roles of enhancer of zeste homolog 2: From skeletal muscle differentiation to rhabdomyosarcoma carcinogenesis

Marchesi

Giordano

Bagella³

2014

Cell Cycle

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“…Levels of PRC2 subunits and its composition are finely regulated during development and cell differentiation; indeed, alterations of their expression or composition are associated to diseases such as cancer (Marchesi & Bagella, ).…”

Section: Polycomb Group Proteins and Cancermentioning

confidence: 99%

The role of enhancer of zeste homolog 2: From viral epigenetics to the carcinogenesis of hepatocellular carcinoma

Sanna

Marchesi

Melone

et al. 2018

Journal Cellular Physiology

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Nowadays, epigenetics covers a crucial role in different fields of science. The enhancer of zeste homolog 2 (EZH2), the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2), is a big proponent of how epigenetic changes can affect the initiation and progression of several diseases. Through its catalytic activity, responsible for the tri-methylation of lysine 27 of the histone H3 (H3K27me3), EZH2 is a good target for both diagnosis and therapy of different pathologies. A large number of studies have demonstrated its crucial role in cancer initiation and progression. Nevertheless, only recently its function in virus diseases has been uncovered; therefore, EZH2 can be an important promoter of viral carcinogenesis. This review explores the role of EZH2 in viral epigenetics based on recent progress that demonstrated the role of this protein in virus environment. In particular, the review focuses on EZH2 behavior in Hepatitis B Virus, analyzing its role in the rise of Hepatocellular Carcinoma.

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Role of Enhancer of Zeste Homolog 2 Polycomb Protein and Its Significance in Tumor Progression and Cell Differentiation

Cited by 8 publications

References 214 publications

Amygdalar expression of the microRNA miR‐101a and its target Ezh2 contribute to rodent anxiety‐like behaviour

Amygdalar expression of the microRNA miR‐101a and its target Ezh2 contribute to rodent anxiety‐like behaviour

Roles of enhancer of zeste homolog 2: From skeletal muscle differentiation to rhabdomyosarcoma carcinogenesis

The role of enhancer of zeste homolog 2: From viral epigenetics to the carcinogenesis of hepatocellular carcinoma

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