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Review
. 2022 Mar 2;15(1):18.
doi: 10.1186/s13045-022-01235-1.

The long and short non-coding RNAs modulating EZH2 signaling in cancer

Sepideh Mirzaei  1 , Mohammad Hossein Gholami  2 , Kiavash Hushmandi  3 , Farid Hashemi  4 , Amirhossein Zabolian  5 , Israel Canadas  6 , Ali Zarrabi  7 , Noushin Nabavi  8 , Amir Reza Aref  9   10 , Francesco Crea  11 , Yuzhuo Wang  12 , Milad Ashrafizadeh  13 , Alan Prem Kumar  14   15
Affiliations
Review

The long and short non-coding RNAs modulating EZH2 signaling in cancer

Sepideh Mirzaei et al. J Hematol Oncol. .

Erratum in

Abstract

Non-coding RNAs (ncRNAs) are a large family of RNA molecules with no capability in encoding proteins. However, they participate in developmental and biological processes and their abnormal expression affects cancer progression. These RNA molecules can function as upstream mediators of different signaling pathways and enhancer of zeste homolog 2 (EZH2) is among them. Briefly, EZH2 belongs to PRCs family and can exert functional roles in cells due to its methyltransferase activity. EZH2 affects gene expression via inducing H3K27me3. In the present review, our aim is to provide a mechanistic discussion of ncRNAs role in regulating EZH2 expression in different cancers. MiRNAs can dually induce/inhibit EZH2 in cancer cells to affect downstream targets such as Wnt, STAT3 and EMT. Furthermore, miRNAs can regulate therapy response of cancer cells via affecting EZH2 signaling. It is noteworthy that EZH2 can reduce miRNA expression by binding to promoter and exerting its methyltransferase activity. Small-interfering RNA (siRNA) and short-hairpin RNA (shRNA) are synthetic, short ncRNAs capable of reducing EZH2 expression and suppressing cancer progression. LncRNAs mainly regulate EZH2 expression via targeting miRNAs. Furthermore, lncRNAs induce EZH2 by modulating miRNA expression. Circular RNAs (CircRNAs), like lncRNAs, affect EZH2 expression via targeting miRNAs. These areas are discussed in the present review with a focus on molecular pathways leading to clinical translation.

Keywords: Cancer therapy; CircRNA; EZH2; LncRNA; MiRNA; ShRNA; SiRNA.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
EZH2 signaling and its role in regulating downstream signaling pathways. Epigenetic regulation of molecular mechanisms in cells such as DNA repair, cell cycle, apoptosis, autophagy and senescence are regulated by EZH2, showing vital functions of this signaling pathway in cells
Fig. 2
Fig. 2
The biogenesis route and functions of miRNAs, siRNA and shRNA in cells [110, 111]
Fig. 3
Fig. 3
MiRNAs regulating EZH2 in different cancers
Fig. 4
Fig. 4
EZH2 as upstream mediator of miRNA expression in cancers. Due to transcriptional role of EZH2, this pathway can target miRNAs in affecting proliferation and invasion of cancer cells that subsequently, determine response of cancer cells to therapy
Fig. 5
Fig. 5
The lncRNA function in cells [268]
Fig. 6
Fig. 6
Regulation of EZH2 by lncRNAs. LncRNAs not only affect EZH2, but also its downstream targets including LAS1, STAT3, Notch1 and Wnt are affected, leading to a significant change in EMT, metastasis and growth of cancer cells
Fig. 7
Fig. 7
The circRNA biogenesis in cells [386]. A canonical splicing; B lariat-driven circularization; C intron-pairing-driven circularization; D bulge–helix–bulge (BHB) motif recognition
Fig. 8
Fig. 8
Regulation of EZH2 by siRNA, shRNA and circRNAs in cancer
See this image and copyright information in PMC

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