Role of lncRNA and EZH2 Interaction/Regulatory Network in Lung Cancer

Abstract

Lung cancer is the leading cause of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts and longer than 200 nucleotides. LncRNAs have been demonstrated to modulate gene expression at transcriptional, post-transcriptional, as well as epigenetic levels in lung cancer. Interestingly, compelling studies have revealed that lncRNAs participated in the EZH2 oncogenic regulatory network. EZH2 plays an important role in the initiation, progression and metastasis of cancer. On one hand, lncRNAs can directly bind to EZH2, recruit EZH2 to the promoter region of genes and repress their expression. On the other hand, lncRNAs can also serve as EZH2 effectors or regulators. In this review, we summarized the types of lncRNA-EZH2 interaction and regulatory network identified till date and discussed their influence on lung cancer. Better understanding regarding the interaction and regulatory network will provide new insights on lncRNA- or EZH2-based therapeutic development in lung cancer.

Ppp1r1b-lncRNA inhibits PRC2 at myogenic regulatory genes to promote cardiac and skeletal muscle development in mouse and human

“…PRC-mediated gene silencing is mainly dependent on the EZH2 dependent H3K27 tri-methylation (Schuettengruber and Cavalli 2009). LncRNAs can directly modulate EZH2 activity or recruit EZH2 to the promoter region of genes to achieve targeted gene repression (Su et al 2018). Moreover, lncRNAs can also serve as EZH2 effectors or regulators (Su et al 2018).…”

“…LncRNAs can directly modulate EZH2 activity or recruit EZH2 to the promoter region of genes to achieve targeted gene repression (Su et al 2018). Moreover, lncRNAs can also serve as EZH2 effectors or regulators (Su et al 2018). For the inhibition of chromatin methylation, a model was suggested that the interactions of PRC2 with lncRNAs and chromatin are mutually antagonistic (Wang et al 2017) and lncRNAs inhibit PRC2 methyltransferase activity by blocking PRC2 binding to targeted chromatin (Beltran et al 2016).…”

LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer

“…Meanwhile, research has shown that negative regulators of Wnt/β-catenin signaling are important for tumor suppression: CXXC4 (CXXC finger protein 4), a negative regulator of Wnt/β-catenin signaling, is reduced by enhancer of zeste homolog 2 (EZH2) in GC 8 9 EZH2 plays an important role in epigenetic regulation of the human genome and is known to be associated with the development of various cancers. 10 Growing evidence has also indicated that Wnt/β-catenin signaling components are regulated by not only long non-coding RNAs (lncRNAs) but also other noncoding classes. 11 12 13 14 15 …”

“… 17 19 20 21 22 23 24 Numerous lncRNAs have been found to contribute to cancer cell functions through silencing of tumor suppressors via interaction with EZH2. 10 A significant number of lncRNAs have been reported to be involved in cancer development by inhibiting tumor suppressor genes through binding with EZH2. 10 25 26 We recently reported that highly expressed lncRNA 12 in esophageal squamous cell carcinoma (HERES) regulate Wnt/β-catenin signaling via interaction with EZH2.…”

“… 10 A significant number of lncRNAs have been reported to be involved in cancer development by inhibiting tumor suppressor genes through binding with EZH2. 10 25 26 We recently reported that highly expressed lncRNA 12 in esophageal squamous cell carcinoma (HERES) regulate Wnt/β-catenin signaling via interaction with EZH2. 12 …”