Enhancer of Zeste Homolog 2 Expression Is Associated With Metastasis and Adverse Clinical Outcome in Clear Cell Renal Cell Carcinoma: A Comparative Study and Review of the Literature

Xu, Bin; Abourbih, Samuel; Sircar, Kanishka; Kassouf, Wassim; Mansure, José João; Aprikian, Armen; Tanguay, Simon; Brimo, Fadi

doi:10.5858/arpa.2012-0525-oa

Cited by 16 publications

(12 citation statements)

References 96 publications

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“…Thus we investigated Ezh2 expression in renal cancer and normal kidney tissues as well as cell lines (HK-2, A-498, 786-O). Similar to a previous report (38), we observed that Ezh2 mRNA expression was significantly higher in renal cancer cell lines and renal cancer tissues compared to normal cells and tissues. Also Ezh2 expression in kidney cancer patients was associated with higher stage and shorter overall survival.…”

Section: Discussionsupporting

confidence: 91%

Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205

et al. 2015

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Recently long non-coding RNAs (lncRNA) have emerged as new gene regulators and prognostic markers in several cancers including renal cell carcinoma (RCC). In this study, we investigated the contributions of the lncRNA MALAT1 in RCC with a specific focus on its transcriptional regulation and its interactions with Ezh2 and miR-205. We found that MALAT1 expression was higher in human RCC tissues where it was associated with reduced patient survival. MALAT1 silencing decreased RCC cell proliferation and invasion and increased apoptosis. Mechanistic investigations showed that MALAT1 was transcriptionally activated by c-Fos and that it interacted with Ezh2. After MALAT1 silencing, E-cadherin expression was increased while beta-catenin expression was decreased through Ezh2. Reciprocal interaction between MALAT1 and miR-205 was also observed. Lastly, MALAT1 bound Ezh2 and oncogenesis facilitated by MALAT1 was inhibited by Ezh2 depletion, thereby blocking epithelial-mesenchyme transition via E-cadherin recovery and beta-catenin downregulation. Overall, our findings illuminate how overexpression of MALAT1 confers an oncogenic function in RCC that may offer a novel theranostic marker in this disease.

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Section: Discussionsupporting

confidence: 91%

Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205

et al. 2015

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“…The association between EZH2 expression and OS was reported in 40 studies enrolling 5,737 patients with various cancer types[ 14 – 18 , 22 – 26 , 31 – 33 , 35 – 37 , 40 , 43 – 51 , 53 – 62 ]. A combined analysis showed that high EZH2 expression predicted poor OS in cancer (HR 1.74, 95% CI: 1.46–2.07; p <0.00001) with significant heterogeneity (I 2 = 83.9%) ( Table 1 and Fig 2 ) .…”

Section: Resultsmentioning

confidence: 99%

Enhancer of Zeste Homolog 2 as an Independent Prognostic Marker for Cancer: A Meta-Analysis

et al. 2015

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BackgroundNovel biomarkers are of particular interest for predicting cancer prognosis. This study aimed to explore the associations between enhancer of zeste homolog 2 (EZH2) and patient survival in various cancers.MethodsRelevant literature was retrieved from PubMed and Web of Science databases. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated.ResultsForty-nine studies (8,050 patients) were included. High EZH2 expression was significantly associated with shorter overall (hazard ratio [HR] 1.74, 95% CI: 1.46–2.07), disease-free (HR 1.59, 95% CI: 1.27–1.99), metastasis-free (HR 2.19, 95% CI: 1.38–3.47), progression-free (HR 2.53, 95% CI: 1.52–4.21), cancer-specific (HR 3.13, 95% CI: 1.70–5.74), and disease-specific (HR 2.29, 95% CI: 1.56–3.35) survival, but not recurrence-free survival (HR 1.38, 95% CI: 0.93–2.06). Moreover, EZH2 expression significantly correlated with distant metastasis (OR 3.25, 95% CI: 1.07–9.87) in esophageal carcinoma; differentiation (OR 3.00, 95% CI: 1.37–6.55) in non-small cell lung cancer; TNM stage (OR 3.18, 95% CI: 2.49–4.08) in renal cell carcinoma; and histological grade (OR 4.50, 95% CI: 3.33–6.09), estrogen receptor status (OR 0.15, 95% CI: 0.11–0.20) and progesterone receptor status (OR 0.30, 95% CI: 0.23–0.39) in breast cancer.ConclusionsOur results suggested that EZH2 might be an independent prognostic factor for multiple survival measures in different cancers.

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“…Ectopic expression of EZH2 in humans can result in several proliferative and neoplastic disorders, including carcinoma, sarcoma, lymphoma, leukemia, and myeloproliferative disorder (Fiskus et al, 2009;Ernst et al, 2010;Xu et al, 2013). Different from PRC2 in animal cells, plant PRC2 shows the ability to promote cell differentiation (Aichinger et al, 2009).…”

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confidence: 99%

CURLY LEAF Regulates Gene Sets Coordinating Seed Size and Lipid Biosynthesis

et al. 2016

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ORCID IDs: 0000-0003-1338-523X (J.L.); 0000-0001-6872-9373 (S.D.).CURLY LEAF (CLF), a histone methyltransferase of Polycomb Repressive Complex 2 (PRC2) for trimethylation of histone H3 Lys 27 (H3K27me3), has been thought as a negative regulator controlling mainly postgermination growth in Arabidopsis (Arabidopsis thaliana). Approximately 14% to 29% of genic regions are decorated by H3K27me3 in the Arabidopsis genome; however, transcriptional repression activities of PRC2 on a majority of these regions remain unclear. Here, by analysis of transcriptome profiles, we found that approximately 11.6% genes in the Arabidopsis genome were repressed by CLF in various organs. Unexpectedly, approximately 54% of these genes were preferentially repressed in siliques. Further analyses of 118 transcriptome datasets uncovered a group of genes that was preferentially expressed and repressed by CLF in embryos at the mature-green stage. This observation suggests that CLF mediates a large-scale H3K27me3 programming/reprogramming event during embryonic development. Plants of clf-28 produced bigger and heavier seeds with higher oil content, larger oil bodies, and altered long-chain fatty acid composition compared with wild type. Around 46% of CLF-repressed genes were associated with H3K27me3 marks; moreover, we verified histone modification and transcriptional repression by CLF on regulatory genes. Our results suggest that CLF silences specific gene expression modules. Genes operating within a module have various molecular functions, but they cooperate to regulate a similar physiological function during embryo development.

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Enhancer of Zeste Homolog 2 Expression Is Associated With Metastasis and Adverse Clinical Outcome in Clear Cell Renal Cell Carcinoma: A Comparative Study and Review of the Literature

Cited by 16 publications

References 96 publications

Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205

Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205

Enhancer of Zeste Homolog 2 as an Independent Prognostic Marker for Cancer: A Meta-Analysis

CURLY LEAF Regulates Gene Sets Coordinating Seed Size and Lipid Biosynthesis

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