Emerging Roles of LncRNAs in the EZH2-regulated Oncogenic Network

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2021 Sep 13

PMID 34512145

Citations 6

Authors

Aixin Hao

Yunxuan Wang

Daniel B Stovall

Yu Wang

Guangchao Sui

Affiliations

Soon will be listed here.

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.

Citing Articles

Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.

Bi L, Wang X, Li J, Li W, Wang Z MedComm (2020). 2025; 6(3):e70080.

PMID: 39991629 PMC: 11843169. DOI: 10.1002/mco2.70080.

LINC00161 upregulated by M2-like tumor-associated macrophages promotes hepatocellular carcinoma progression by methylating HACE1 promoters.

Zhang Y, Chen S, You L, He Z, Xu P, Huang W Cytotechnology. 2024; 76(6):777-793.

PMID: 39435425 PMC: 11490593. DOI: 10.1007/s10616-024-00653-y.

microRNA 21 and long non-coding RNAs interplays underlie cancer pathophysiology: A narrative review.

Giordo R, Ahmadi F, Husaini N, Al-Nuaimi N, Ahmad S, Pintus G Noncoding RNA Res. 2024; 9(3):831-852.

PMID: 38586315 PMC: 10995982. DOI: 10.1016/j.ncrna.2024.03.013.

Biological functions and applications of LncRNAs in the regulation of the extracellular matrix in osteoarthritis.

Shi D, Mei Y, Hao W, Li J, Liu S, Lin X Front Cell Dev Biol. 2024; 11:1330624.

PMID: 38259516 PMC: 10800956. DOI: 10.3389/fcell.2023.1330624.

In Vivo and In Vitro Characterization of the RNA Binding Capacity of SETD1A (KMT2F).

Amin H, Szabo B, Abukhairan R, Zeke A, Kardos J, Schad E Int J Mol Sci. 2023; 24(22).

PMID: 38003223 PMC: 10671326. DOI: 10.3390/ijms242216032.

References

Zhu B, Cui H, Xu W . Hydrogen inhibits the proliferation and migration of gastric cancer cells by modulating lncRNA MALAT1/miR-124-3p/EZH2 axis. Cancer Cell Int. 2021; 21(1):70. PMC: 7821405. DOI: 10.1186/s12935-020-01743-5. View

Wang X, Ruan Y, Wang X, Zhao W, Jiang Q, Jiang C . Long intragenic non-coding RNA lincRNA-p21 suppresses development of human prostate cancer. Cell Prolif. 2016; 50(2). PMC: 6529152. DOI: 10.1111/cpr.12318. View

Zhou L, Tian Y, Guo F, Yu B, Li J, Xu H . LincRNA-p21 knockdown reversed tumor-associated macrophages function by promoting MDM2 to antagonize* p53 activation and alleviate breast cancer development. Cancer Immunol Immunother. 2020; 69(5):835-846. PMC: 11027865. DOI: 10.1007/s00262-020-02511-0. View

Wang X, Goodrich K, Gooding A, Naeem H, Archer S, Paucek R . Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines. Mol Cell. 2017; 65(6):1056-1067.e5. DOI: 10.1016/j.molcel.2017.02.003. View

Baylin S, Jones P . A decade of exploring the cancer epigenome - biological and translational implications. Nat Rev Cancer. 2011; 11(10):726-34. PMC: 3307543. DOI: 10.1038/nrc3130. View

Zhou X, Gao W, Hua H, Ji Z . LncRNA-BLACAT1 Facilitates Proliferation, Migration and Aerobic Glycolysis of Pancreatic Cancer Cells by Repressing CDKN1C via EZH2-Induced H3K27me3. Front Oncol. 2020; 10:539805. PMC: 7538708. DOI: 10.3389/fonc.2020.539805. View

Buske F, Bauer D, Mattick J, Bailey T . Triplexator: detecting nucleic acid triple helices in genomic and transcriptomic data. Genome Res. 2012; 22(7):1372-81. PMC: 3396377. DOI: 10.1101/gr.130237.111. View

Lee J, Lee J, Kim H, Kim K, Park H, Kim J . EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4 E3 ubiquitin ligase complex. Mol Cell. 2012; 48(4):572-86. DOI: 10.1016/j.molcel.2012.09.004. View

Zhang J, Li W, Yang Y, Yan L, Zhang S, He J . LncRNA XIST facilitates cell growth, migration and invasion via modulating H3 histone methylation of DKK1 in neuroblastoma. Cell Cycle. 2019; 18(16):1882-1892. PMC: 6681787. DOI: 10.1080/15384101.2019.1632134. View

10.

Wang J, Yang X, Li R, Zhang R, Hu D, Zhang Y . LncRNA SNHG6 Inhibits Apoptosis by Regulating EZH2 Expression via the Sponging of MiR-101-3p in Esophageal Squamous-Cell Carcinoma. Onco Targets Ther. 2020; 13:11411-11420. PMC: 7656962. DOI: 10.2147/OTT.S275135. View

11.

Wang K, Chang H . Molecular mechanisms of long noncoding RNAs. Mol Cell. 2011; 43(6):904-14. PMC: 3199020. DOI: 10.1016/j.molcel.2011.08.018. View

12.

Haig D . The (dual) origin of epigenetics. Cold Spring Harb Symp Quant Biol. 2005; 69:67-70. DOI: 10.1101/sqb.2004.69.67. View

13.

Rajabi H, Hiraki M, Tagde A, Alam M, Bouillez A, Christensen C . MUC1-C activates EZH2 expression and function in human cancer cells. Sci Rep. 2017; 7(1):7481. PMC: 5547076. DOI: 10.1038/s41598-017-07850-0. View

14.

Zhang F, Peng H . LncRNA-ANCR regulates the cell growth of osteosarcoma by interacting with EZH2 and affecting the expression of p21 and p27. J Orthop Surg Res. 2017; 12(1):103. PMC: 5499053. DOI: 10.1186/s13018-017-0599-7. View

15.

Li Y, Li D, Zhao M, Huang S, Zhang Q, Lin H . Long noncoding RNA SNHG6 regulates p21 expression via activation of the JNK pathway and regulation of EZH2 in gastric cancer cells. Life Sci. 2018; 208:295-304. DOI: 10.1016/j.lfs.2018.07.032. View

16.

Wan L, Sun M, Liu G, Wei C, Zhang E, Kong R . Long Noncoding RNA PVT1 Promotes Non-Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression. Mol Cancer Ther. 2016; 15(5):1082-94. DOI: 10.1158/1535-7163.MCT-15-0707. View

17.

Guo J, Hao C, Wang C, Li L . Long noncoding RNA PVT1 modulates hepatocellular carcinoma cell proliferation and apoptosis by recruiting EZH2. Cancer Cell Int. 2018; 18:98. PMC: 6042336. DOI: 10.1186/s12935-018-0582-3. View

18.

Cheng C, Dong Y, Ru X, Xia Y, Ji Y . LncRNA ANCR promotes glioma cells invasion, migration, proliferation and inhibits apoptosis via interacting with EZH2 and repressing PTEN expression. Cancer Gene Ther. 2020; 28(9):1025-1034. DOI: 10.1038/s41417-020-00263-8. View

19.

Ryan R, Nitta M, Borger D, Zukerberg L, Ferry J, Lee Harris N . EZH2 codon 641 mutations are common in BCL2-rearranged germinal center B cell lymphomas. PLoS One. 2011; 6(12):e28585. PMC: 3237460. DOI: 10.1371/journal.pone.0028585. View

20.

Dawson M, Kouzarides T . Cancer epigenetics: from mechanism to therapy. Cell. 2012; 150(1):12-27. DOI: 10.1016/j.cell.2012.06.013. View