Long Noncoding RNA-EBIC Promotes Tumor Cell Invasion by Binding to EZH2 and Repressing E-Cadherin in Cervical Cancer

Abstract

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to play key roles in tumorgenesis. However, the contributions of lncRNAs to cervical cancer (CC) remain largely unknown. In this study, differentially expressed lncRNAs and mRNAs in cervical cancer and paired peritumoral tissues were detected by transcriptome microarray analysis. We found 708 probe sets of lncRNAs increased and 836 probe sets decreased in CC tissues, while 1288 mRNA differential probe sets increased and 901 mRNA probe sets decreased. The results were validated by quantitative real-time polymerase chain reaction (qPCR). Then, we found a specific differentially expressed lncRNA can physically bind to enhancer of zeste homolog2 (EZH2) by using RNA immunoprecipitation. We termed it as EZH2-binding lncRNA in cervical cancer [lncRNA-EBIC]. Wound healing assays and Matrigel invasion assays were used to determine the function of this lncRNA by silencing it. We observed that the migration and invasion of cervical cancer cells in vitro were inhibited upon suppression of lncRNA-EBIC by siRNA. We also found that the association between lncRNA-EBIC and EZH2 was required for the repression of E-cadherin, which was a key molecular in the metastasis of cervical cancer.ConclusionThese results demonstrated that lncRNA-EBIC was an oncogenic lncRNA, which could promote tumor cell invasion in CC by binding to EZH2 and inhibiting E-cadherin expression.

Long Noncoding RNA MALAT1 Promotes Aggressive Renal Cell Carcinoma through Ezh2 and Interacts with miR-205

“…Several long non-coding RNAs such as H19 and EBIC have been found to bind to Ezh2 in other cancers (28, 29). MALAT1 has been reported to bind to Suz12, a component of PRC2 in bladder cancer cell lines (30).…”

Sunitinib Dose Escalation Overcomes Transient Resistance in Clear Cell Renal Cell Carcinoma and Is Associated with Epigenetic Modifications

“…Similarly, mechanistic studies suggest that inhibition of EZH2 expression or activity sensitized ccRCC cells to sunitinib in vitro and provide a rationale for a potential role of EZH2 in modulating tumor response and resistance to sunitinib treatment. A downstream target of EZH2 such as E-cadherin was increased with decrease in EZH2 which was also accompanied by a decrease in E2F-1 (31). E2F-1 has been reported in previous studies to play a role in multidrug resistance and negatively regulating cell proliferation when overexpressed (32).…”

The recruitment of chromatin modifiers by long noncoding RNAs: lessons from PRC2

“…In the case of PRC2, binding motifs could not explain the association of the protein complex with thousands of RNA transcripts, as observed by immunoprecipitation-based approaches (Rinn et al 2007;Zhao et al 2008Zhao et al , 2010Guttman et al 2011;Heo and Sung 2011;Kotake et al 2011;Shore et al 2012;He et al 2013;Klattenhoff et al 2013;Sun et al 2014). In vivo CLIP and PAR-CLIP experiments for EZH2 (Guil et al 2012;Kaneko et al 2013) or JARID2 (Kaneko et al 2014a) did not result in well-defined peaks that could, in principle, lead to the discovery of binding motifs.…”