Scholarlink

<p>Hepatoblastoma (HB) is the most common pediatric liver malignancy. However, its cellular origin and molecular drivers remain poorly defined. Using single-nuclear RNA sequencing (snRNA-seq), we identified a proliferative, hepatocyte-derived tumor cell population (cycling Hep<sub>T</sub>) enriched for Enhancer of Zeste Homolog 2 (<i>EZH2)</i> expression, particularly in the aggressive embryonal subtype. Integrative genomic and transcriptomic profiling confirmed <i>EZH2</i> overexpression. Disruption of the PRC2 complex was evident through mislocalization and reduced expression of SUZ12, a core component. <i>EZH2</i> overexpression correlated with upregulation of mitotic regulators such as <i>AURKB</i> and <i>Ki67</i> in human HB gene expression analysis as compared to background liver. Targeted sequencing identified variants of uncertain significance in <i>EZH2</i> and <i>SUZ12</i> in 11 of 11 patient tumors. Pharmacologic inhibition of EZH2 with EPZ-6438 reduced proliferation and sensitized HB cells to cisplatin through gene regulation, potentially modulating platinum accumulation both in vitro and in vivo. In summary, EZH2 promotes HB progression through epigenetic silencing and noncanonical signaling pathways. These findings support EZH2’s contribution to HB pathogenesis, therefore identifying it as a novel therapeutic target.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Investigating the oncogenic role of aberrant EZH2 in hepatoblastoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月6日

查看全文
  • Kathryn Glaser,
  • Erica A. K. DePasquale,
  • Lara Berklite,
  • Brian T. Hickner,
  • Priyanka Rao,
  • Roma H. Patel,
  • Andrew A. Badachhape,
  • Somak Roy,
  • Emily Schepers,
  • Nikolai A. Timchenko,
  • James I. Geller,
  • Sarangarajan Ranganathan,
  • Gregory M. Tiao,
  • Bruce Aronow,
  • Takanori Takebe,
  • Sarah E. Woodfield,
  • Sanjeev A. Vasudevan,
  • Alexander J. Bondoc

摘要

Hepatoblastoma (HB) is the most common pediatric liver malignancy. However, its cellular origin and molecular drivers remain poorly defined. Using single-nuclear RNA sequencing (snRNA-seq), we identified a proliferative, hepatocyte-derived tumor cell population (cycling HepT) enriched for Enhancer of Zeste Homolog 2 (EZH2) expression, particularly in the aggressive embryonal subtype. Integrative genomic and transcriptomic profiling confirmed EZH2 overexpression. Disruption of the PRC2 complex was evident through mislocalization and reduced expression of SUZ12, a core component. EZH2 overexpression correlated with upregulation of mitotic regulators such as AURKB and Ki67 in human HB gene expression analysis as compared to background liver. Targeted sequencing identified variants of uncertain significance in EZH2 and SUZ12 in 11 of 11 patient tumors. Pharmacologic inhibition of EZH2 with EPZ-6438 reduced proliferation and sensitized HB cells to cisplatin through gene regulation, potentially modulating platinum accumulation both in vitro and in vivo. In summary, EZH2 promotes HB progression through epigenetic silencing and noncanonical signaling pathways. These findings support EZH2’s contribution to HB pathogenesis, therefore identifying it as a novel therapeutic target.