Int J Biol Sci 2021; 17(13):3268-3280. doi:10.7150/ijbs.63488 This issue


Emerging Roles of LncRNAs in the EZH2-regulated Oncogenic Network

Aixin Hao1, Yunxuan Wang2, Daniel B. Stovall3, Yu Wang1✉, Guangchao Sui1✉

1. Key Laboratory of Saline-alkali Vegetation Ecology Restoration, Ministry of Education, College of Life Science, Northeast Forestry University, Harbin 150040, China
2. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, 150081, China
3. College of Arts and Sciences, Winthrop University, Rock Hill, SC 29733, the United States

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Hao A, Wang Y, Stovall DB, Wang Y, Sui G. Emerging Roles of LncRNAs in the EZH2-regulated Oncogenic Network. Int J Biol Sci 2021; 17(13):3268-3280. doi:10.7150/ijbs.63488. Available from

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Graphic abstract

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.

Keywords: cancer, lncRNA, EZH2, PRC2, H3K27me3, non-histone methylation, epigenetic regulation