Long Noncoding RNA EZR-AS1 Regulates the Proliferation, Migration, and Apoptosis of Human Venous Endothelial Cells via SMYD3.

Numerous studies have shown that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of human cardiovascular diseases. However, whether lncRNA ezrin antisense RNA 1 (EZR-AS1) is associated with the progression of coronary heart disease (CHD) remains unclear. Accordingly, the aim of the present study was to evaluate the role of lncRNA EZR-AS1 in patients with CHD and in human venous endothelial cells (HUVECs). The findings revealed that lncRNA EZR-AS1 was highly expressed in the peripheral blood of patients with CHD. In vitro experiments showed that the overexpression of EZR-AS1 could enhance proliferation, migration, and apoptosis by upregulating the expression of EZR in HUVECs; downregulation of lncRNA EZR-AS1 resulted in the opposite effect. lncRNA EZR-AS1 was also found to regulate SET and MYND domain-containing protein 3 (SMYD3), a histone H3 lysine 4-specific methyltransferase, which subsequently mediated EZR transcription. Collectively, these results demonstrate that lncRNA EZR-AS1 plays an important role in HUVECs function via SMYD3 signaling.

You G ，Long X ，Song F ，Huang J ，Tian M ，Xiao Y ，Deng S ，Wu Q ... -  《-》

The interaction of lncRNA EZR-AS1 with SMYD3 maintains overexpression of EZR in ESCC cells.

Zhang XD ，Huang GW ，Xie YH ，He JZ ，Guo JC ，Xu XE ，Liao LD ，Xie YM ，Song YM ，Li EM ，Xu LY ... -  《-》

Silencing of lncRNA EZR-AS1 inhibits proliferation, invasion, and migration of colorectal cancer cells through blocking transforming growth factor β signaling.

Long non-coding RNA (lncRNA) plays a key regulatory role in the pathogenesis of colorectal cancer (CRC). In the present study, the specific regulatory role of lncRNA ezrin antisense RNA 1 (EZR-AS1) on CRC was investigated. The expression of lncRNA EZR-AS1 was significantly up-regulated in CRC cell lines (HCT8, HCT116, HT29, and SW620 cells), which was significantly different from that of normal human fetal colonic mucosa cells (FHC cells) (P<0.01). HCT116 and HT29 cells were then transfected with EZR-AS1 shRNA (sh-EZR-AS1) to silence lncRNA EZR-AS1 (P<0.01). When compared with the Control, after transfection of SH-EZR-AS1, E-cadherin was up-regulated, Vimentin was down-regulated, the apoptosis rate was increased, the cell viability, wound healing rate, and the number of invasive cells were decreased in HCT116 and HT29 cells (P<0.05). Silencing of lncRNA EZR-AS also significantly reduced the tumor volume and weight in mice injected with sh-EZR-AS1-transfected HCT116 and HT29 cells (P<0.05). The regulatory relationship between lncRNA EZR-AS1 and transforming growth factor β (TGF-β) signaling was further identified in CRC cells. Silencing of lncRNA EZR-AS1 significantly down-regulated TGF-β, Smad2, and α-SMA expression in HCT116 and HT29 cells at the protein level (P<0.05). The intervention of SB431542 (a TGF-β receptor blocker) and silencing of Smad2 both significantly down-regulated lncRNA EZR-AS1 expression in HCT116 and HT29 cells (P<0.01). In conclusion, silencing of lncRNA EZR-AS1 inhibited the proliferation, invasion, migration, and epithelial-mesenchymal transition, and promoted the apoptosis of CRC cells through blocking TGF-β signaling.

Liu Z ，Wang N ，Wang F ，Zhang S ，Ding J ... -  《-》

Long noncoding RNA EZR-AS1 promotes tumor growth and metastasis by modulating Wnt/β-catenin pathway in breast cancer.

Bai Y ，Zhou X ，Huang L ，Wan Y ，Li X ，Wang Y ... -  《-》

Long noncoding RNA ANRIL regulates endothelial cell activities associated with coronary artery disease by up-regulating CLIP1, EZR, and LYVE1 genes.

Coronary artery disease (CAD) is the leading cause of death worldwide. Long noncoding RNAs (lncRNAs) are a class of noncoding transcripts of > 200 nucleotides and are increasingly recognized as playing functional roles in physiology and disease. ANRIL is an lncRNA gene mapped to the chromosome 9p21 genetic locus for CAD identified by the first series of genome-wide association studies (GWAS). However, ANRIL's role in CAD and the underlying molecular mechanism are unknown. Here, we show that the major ANRIL transcript in endothelial cells (ECs) is DQ485454 with a much higher expression level in ECs than in THP-1 monocytes. Of note, DQ485454 expression was down-regulated in CAD coronary arteries compared with non-CAD arteries. DQ485454 overexpression significantly reduced monocyte adhesion to ECs, transendothelial monocyte migration (TEM), and EC migration, which are critical cellular processes involved in CAD initiation, whereas siRNA-mediated ANRIL knockdown (KD) had the opposite effect. Microarray and follow-up quantitative RT-PCR analyses revealed that the ANRIL KD down-regulated expression of AHNAK2, CLIP1, CXCL11, ENC1, EZR, LYVE1, WASL, and TNFSF10 genes and up-regulated TMEM100 and TMEM106B genes. Mechanistic studies disclosed that overexpression of CLIP1, EZR, and LYVE1 reversed the effects of ANRIL KD on monocyte adhesion to ECs, TEM, and EC migration. These findings indicate that ANRIL regulates EC functions directly related to CAD, supporting the hypothesis that ANRIL is involved in CAD pathogenesis at the 9p21 genetic locus and identifying a molecular mechanism underlying lncRNA-mediated regulation of EC function and CAD development.

Cho H ，Shen GQ ，Wang X ，Wang F ，Archacki S ，Li Y ，Yu G ，Chakrabarti S ，Chen Q ，Wang QK ... -  《-》