Tu1741 RNA-Binding Protein HuR Enhances Translation of E-Cadherin and Modulates Epithelial Barrier Function

2013 ◽  
Vol 144 (5) ◽  
pp. S-834-S-835
Author(s):  
Tingxi Yu ◽  
Bei-Lin Gu ◽  
Wei Cai
Keyword(s):  
Barrier Function ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
E Cadherin

scholarly journals H19Long Noncoding RNA Regulates Intestinal Epithelial Barrier Function via MicroRNA 675 by Interacting with RNA-Binding Protein HuR

2016 ◽  
Vol 36 (9) ◽  
pp. 1332-1341 ◽  
Author(s):  
Tongtong Zou ◽  
Suraj K. Jaladanki ◽  
Lan Liu ◽  
Lan Xiao ◽  
Hee Kyoung Chung ◽  
...  
Keyword(s):  
Barrier Function ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function ◽  
E Cadherin

The disruption of the intestinal epithelial barrier function occurs commonly in various pathologies, but the exact mechanisms responsible are unclear. TheH19long noncoding RNA (lncRNA) regulates the expression of different genes and has been implicated in human genetic disorders and cancer. Here, we report thatH19plays an important role in controlling the intestinal epithelial barrier function by serving as a precursor for microRNA 675 (miR-675).H19overexpression increased the cellular abundance of miR-675, which in turn destabilized and repressed the translation of mRNAs encoding tight junction protein ZO-1 and adherens junction E-cadherin, resulting in the dysfunction of the epithelial barrier. Increasing the level of the RNA-binding protein HuR in cells overexpressingH19prevented the stimulation of miR-675 processing fromH19, promoted ZO-1 and E-cadherin expression, and restored the epithelial barrier function to a nearly normal level. In contrast, the targeted deletion of HuR in intestinal epithelial cells enhanced miR-675 production in the mucosa and delayed the recovery of the gut barrier function after exposure to mesenteric ischemia/reperfusion. These results indicate thatH19interacts with HuR and regulates the intestinal epithelial barrier function via theH19-encoded miR-675 by altering ZO-1 and E-cadherin expression posttranscriptionally.

scholarly journals JunD Represses Transcription and Translation of the Tight Junction Protein Zona Occludens-1 Modulating Intestinal Epithelial Barrier Function

2008 ◽  
Vol 19 (9) ◽  
pp. 3701-3712 ◽  
Author(s):  
Jie Chen ◽  
Lan Xiao ◽  
Jaladanki N. Rao ◽  
Tongtong Zou ◽  
Lan Liu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Binding Protein ◽  
Mrna Translation ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function

The AP-1 transcription factor JunD is highly expressed in intestinal epithelial cells, but its exact role in maintaining the integrity of intestinal epithelial barrier remains unknown. The tight junction (TJ) protein zonula occludens (ZO)-1 links the intracellular domain of TJ-transmembrane proteins occludin, claudins, and junctional adhesion molecules to many cytoplasmic proteins and the actin cytoskeleton and is crucial for assembly of the TJ complex. Here, we show that JunD negatively regulates expression of ZO-1 and is implicated in the regulation of intestinal epithelial barrier function. Increased JunD levels by ectopic overexpression of the junD gene or by depleting cellular polyamines repressed ZO-1 expression and increased epithelial paracellular permeability. JunD regulated ZO-1 expression at the levels of transcription and translation. Transcriptional repression of ZO-1 by JunD was mediated through cAMP response element-binding protein-binding site within its proximal region of the ZO-1-promoter, whereas induced JunD inhibited ZO-1 mRNA translation by enhancing the interaction of the ZO-1 3′-untranslated region with RNA-binding protein T cell-restricted intracellular antigen 1-related protein. These results indicate that JunD is a biological suppressor of ZO-1 expression in intestinal epithelial cells and plays a critical role in maintaining epithelial barrier function.

scholarly journals CUGBP1 and HuR regulate E-cadherin translation by altering recruitment of E-cadherin mRNA to processing bodies and modulate epithelial barrier function

2016 ◽  
Vol 310 (1) ◽  
pp. C54-C65 ◽  
Author(s):  
Ting-Xi Yu ◽  
Bei-Lin Gu ◽  
Jun-Kai Yan ◽  
Jie Zhu ◽  
Wei-Hui Yan ◽  
...  
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Intestinal Barrier ◽  
Primary Component ◽  
Epithelial Barrier ◽  
Barrier Dysfunction ◽  
Processing Bodies ◽  
Epithelial Barrier Function ◽  
Epithelial Barrier Dysfunction ◽  
E Cadherin

The effectiveness and stability of epithelial barrier depend on apical junctional complexes, which consist of tight junctions (TJs) and adherens junctions (AJs). E-cadherin is the primary component of AJs, and it is essential for maintenance of cell-to-cell interactions and regulates the epithelial barrier. However, the exact mechanism underlying E-cadherin expression, particularly at the posttranscriptional level, remains largely unknown. RNA-binding proteins CUG-binding protein 1 (CUGBP1) and HU antigen R (HuR) are highly expressed in the intestinal epithelial tissues and modulate the stability and translation of target mRNAs. Here, we present evidence that CUGBP1 and HuR interact directly with the 3′-untranslated region of E-cadherin mRNA and regulate E-cadherin translation. CUGBP1 overexpression in Caco-2 cells inhibited E-cadherin translation by increasing the recruitment of E-cadherin mRNA to processing bodies (PBs), thus resulting in an increase in paracellular permeability. Overexpression of HuR exhibited an opposite effect on E-cadherin expression by preventing the translocation of E-cadherin mRNA to PBs and therefore prevented CUGBP1-induced repression of E-cadherin expression. Elevation of HuR also abolished the CUGBP1-induced epithelial barrier dysfunction. These findings indicate that CUGBP1 and HuR negate each other's effects in regulating E-cadherin translation by altering the recruitment of E-cadherin mRNA to PBs and play an important role in the regulation of intestinal barrier integrity under various pathophysiological conditions.

scholarly journals The RNA-binding protein quaking maintains endothelial barrier function and affects VE-cadherin and β-catenin protein expression

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ruben G. de Bruin ◽  
Eric P. van der Veer ◽  
Jurriën Prins ◽  
Dae Hyun Lee ◽  
Martijn J. C. Dane ◽  
...  
Keyword(s):  
Protein Expression ◽  
Barrier Function ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function

scholarly journals Hyaluronan and Layilin Mediate Loss of Airway Epithelial Barrier Function Induced by Cigarette Smoke by Decreasing E-cadherin

2012 ◽  
Vol 287 (50) ◽  
pp. 42288-42298 ◽  
Author(s):  
Rosanna Malbran Forteza ◽  
S. Marina Casalino-Matsuda ◽  
Nieves S. Falcon ◽  
Monica Valencia Gattas ◽  
Maria E. Monzon
Keyword(s):  
Cigarette Smoke ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
Airway Epithelial ◽  
Epithelial Barrier Function ◽  
E Cadherin

scholarly journals LncRNA SNHG1 and RNA Binding Protein hnRNPL form a Complex and Coregulate CDH1 to Boost the Growth and Metastasis of Prostate Cancer

2020 ◽  
Author(s):  
Xiao Tan ◽  
Wen-Bin Chen ◽  
Dao-Jun Lv ◽  
Tao-Wei Yang ◽  
Kai-Hui Wu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Rna Binding ◽  
Epithelial Mesenchymal Transition ◽  
Binding Protein ◽  
Expression Profiles ◽  
Mrna Level ◽  
Rna Binding Protein ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
E Cadherin

Abstract Background: The interaction between LncRNA and RNA-binding protein (RBPs) plays an essential role in the regulation over the malignant progression of tumors. Previous studies on the mechanism of SNHG1, an emerging lncRNA, have primarily focused on the competing endogenous RNA (ceRNA) mechanism. Nevertheless, the underlying mechanism between SNHG1 and RBPs in tumors remains to be explored, especially in prostate cancer (PCa).Methods：SNHG1 expression profiles in PCa were determined through the analysis of TCGA data and tissue microarray at the mRNA level. Gain- and loss-of-function experiments were performed to investigate the biological role of SNHG1 in PCa initiation and progression. RNA-seq, immunoblotting, RNA pull-down and RNA immunoprecipitation analyses were utilized to clarify potential pathways with which SNHG1 might be involved. Finally, rescue experiments were carried out to further confirm this mechanism.Results: We found that SNHG1 was dominantly expressed in the nuclei of PCa cells and significantly upregulated in PCa patients. The higher expression level of SNHG1 was dramatically correlated with tumor metastasis and patient survival. Functionally, overexpression of SNHG1 in PCa cells induced epithelial–mesenchymal transition (EMT), accompanied by down-regulation of the epithelial marker, E-cadherin, and up-regulation of the mesenchymal marker, vimentin. Increased proliferation and migration, as well as accelerated xenograft tumor growth, were observed in SNHG1-overexpressing PCa cells, while opposite effects were achieved in SNHG1-silenced cells. Mechanistically, SNHG1 competitively interacted with hnRNPL to impair the translation of protein E-cadherin, thus activating the effect of SNHG1 on the EMT pathway, eventually promoting the metastasis of PCa. Conclusion: Our findings demonstrate that SNHG1 is a positive regulator of EMT activation through the SNHG1-hnRNPL-CDH1 axis. SNHG1 may serve as a novel potential therapeutic target for PCa.

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