Scholarlink

<p>The polycomb protein EZH2 is up-regulated in Chronic Myeloid Leukaemia (CML) and associated with transcriptional reprogramming. Here we tested whether EZH2 might also act as a modulator of the mRNA splicing landscape to elicit its oncogenic function in CML. We treated CML cell lines with EZH2 inhibitors and detected differential splicing of several hundreds of events, potentially caused by the transcriptional regulation of splicing factors. Amongst those genes, CELF2 was identified as a candidate to mediate part of the EZH2 inhibitor induced phenotype. Upon over-expression, we observed (1) reduced cell growth, viability, and colony formation of CML cell lines, (2) a change in the splicing landscape, partially overlapping with EZH2 mediated changes, (3) the down-regulation of MYC signalling. Importantly, these findings were successfully validated in a cohort of CML patient samples, confirming the role of CELF2 as EZH2-regulated tumour-suppressor, contributing to the severe splicing de-regulation present in CML. Based on this we propose that EZH2 exerts part of its oncogenic function in CML through the transcriptional repression of splicing factors. Finally, analysis of publicly available datasets suggests that splicing modulation by EZH2 might not be restricted to CML.</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

EZH2 modulates mRNA splicing and exerts part of its oncogenic function through repression of splicing factors in CML

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年1月7日

查看全文
  • Reinhard Brunmeir,
  • Li Ying,
  • Junli Yan,
  • Yan Ting Hee,
  • Baohong Lin,
  • Harvinder Kaur,
  • Qiao Zheng Leong,
  • Wei Wen Teo,
  • Gerald Choong,
  • Wei-Ying Jen,
  • Liang Piu Koh,
  • Lip Kun Tan,
  • Esther Chan,
  • Melissa Ooi,
  • Henry Yang,
  • Wee Joo Chng

摘要

The polycomb protein EZH2 is up-regulated in Chronic Myeloid Leukaemia (CML) and associated with transcriptional reprogramming. Here we tested whether EZH2 might also act as a modulator of the mRNA splicing landscape to elicit its oncogenic function in CML. We treated CML cell lines with EZH2 inhibitors and detected differential splicing of several hundreds of events, potentially caused by the transcriptional regulation of splicing factors. Amongst those genes, CELF2 was identified as a candidate to mediate part of the EZH2 inhibitor induced phenotype. Upon over-expression, we observed (1) reduced cell growth, viability, and colony formation of CML cell lines, (2) a change in the splicing landscape, partially overlapping with EZH2 mediated changes, (3) the down-regulation of MYC signalling. Importantly, these findings were successfully validated in a cohort of CML patient samples, confirming the role of CELF2 as EZH2-regulated tumour-suppressor, contributing to the severe splicing de-regulation present in CML. Based on this we propose that EZH2 exerts part of its oncogenic function in CML through the transcriptional repression of splicing factors. Finally, analysis of publicly available datasets suggests that splicing modulation by EZH2 might not be restricted to CML.