Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin 150040, China.
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Int J Biol Sci. 2021 Jul 25;17(13):3268-3280. doi: 10.7150/ijbs.63488. eCollection 2021.
Cancer is a life-threatening disease, but cancer therapies based on epigenetic mechanisms have made great progress. Enhancer of zeste homolog 2 (EZH2) is the key catalytic component of Polycomb repressive complex 2 (PRC2) that mediates the tri-methylation of lysine 27 on histone 3 (H3K27me3), a well-recognized marker of transcriptional repression. Mounting evidence indicates that EZH2 is elevated in various cancers and associates with poor prognosis. In addition, many studies revealed that EZH2 is also involved in transcriptional repression dependent or independent of PRC2. Meanwhile, long non-coding RNAs (lncRNAs) have been reported to regulate numerous and diverse signaling pathways in oncogenesis. In this review, we firstly discuss functional interactions between EZH2 and lncRNAs that determine PRC2-dependent and -independent roles of EZH2. Secondly, we summarize the lncRNAs regulating EZH2 expression at transcription, post-transcription and post-translation levels. Thirdly, we review several oncogenic pathways cooperatively regulated by lncRNAs and EZH2, including the Wnt/β-catenin and p53 pathways. In conclusion, lncRNAs play a key role in the EZH2-regulated oncogenic network with many fertile directions to be explored.
癌症是一种危及生命的疾病，但基于表观遗传机制的癌症疗法已经取得了重大进展。EZH2（ Enhancer of zeste homolog 2 ）是 Polycomb 抑制复合物 2（PRC2）的关键催化组成部分，介导组蛋白 3（H3K27me3）赖氨酸 27 的三甲基化，这是转录抑制的公认标志。越来越多的证据表明，EZH2 在各种癌症中升高，并与不良预后相关。此外，许多研究表明，EZH2 还参与 PRC2 依赖和独立的转录抑制。同时，长链非编码 RNA（lncRNA）已被报道可调节致癌作用中的许多不同的信号通路。在这篇综述中，我们首先讨论了 EZH2 和 lncRNA 之间的功能相互作用，这些相互作用决定了 EZH2 的 PRC2 依赖和独立作用。其次，我们总结了在转录、转录后和翻译后水平调节 EZH2 表达的 lncRNA。第三，我们综述了 lncRNA 和 EZH2 共同调节的几个致癌途径，包括 Wnt/β-catenin 和 p53 途径。总之，lncRNA 在 EZH2 调节的致癌网络中发挥着关键作用，有许多富有成效的方向有待探索。
