Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan.
Sci Rep. 2013;3:1911. doi: 10.1038/srep01911.
Small cell lung cancer (SCLC) is a subtype of lung cancer with poor prognosis. Expression array analysis of 23 SCLC cases and 42 normal tissues revealed that EZH2 and other PRC2 members were highly expressed in SCLC. ChIP-seq for H3K27me3 suggested that genes with H3K27me3(+) in SCLC were extended not only to PRC2-target genes in ES cells but also to other target genes such as cellular adhesion-related genes. These H3K27me3(+) genes in SCLC were repressed significantly, and introduction of the most repressed gene JUB into SCLC cell line lead to growth inhibition. Shorter overall survival of clinical SCLC cases correlated to repression of JUB alone, or a set of four genes including H3K27me3(+) genes. Treatment with EZH2 inhibitors, DZNep and GSK126, resulted in growth repression of SCLC cell lines. High PRC2 expression was suggested to contribute to gene repression in SCLC, and may play a role in genesis of SCLC.
小细胞肺癌（SCLC）是一种预后不良的肺癌亚型。对 23 例 SCLC 病例和 42 例正常组织的表达谱分析显示，EZH2 和其他 PRC2 成员在 SCLC 中高表达。H3K27me3 的 ChIP-seq 表明，SCLC 中具有 H3K27me3(+)的基因不仅扩展到 ES 细胞中 PRC2 的靶基因，而且扩展到其他靶基因，如细胞黏附相关基因。这些 SCLC 中的 H3K27me3(+)基因受到显著抑制，将最受抑制的基因 JUB 导入 SCLC 细胞系导致生长抑制。临床 SCLC 病例的总生存期较短与 JUB 单独的抑制，或包括 H3K27me3(+)基因在内的四个基因的一组相关。EZH2 抑制剂 DZNep 和 GSK126 的治疗导致 SCLC 细胞系的生长抑制。高 PRC2 表达提示其可能在 SCLC 基因抑制中发挥作用，并可能在 SCLC 的发生中发挥作用。
